Buster Keaton remained insulated within the professional sphere of vaudeville throughout his early life. He continued his tenure with his family at venues like the National in Boston in 1914. Although the physical exertion required for their signature knockabout routines became increasingly taxing due to Joe Keaton's advancing age and Buster's own increase in height and weight, the performances remained fundamentally unchanged, persisting in the same rigorous vein day after day. During this period, the family act had also been reduced in scale as Buster's younger siblings, Harry and Louise, were no longer participants. They were withdrawn from the stage and sent away to boarding schools. 1914 marked the cinematic debut of Charlie Chaplin's iconic "Little Tramp" persona in Kid Auto Races at Venice, while Roscoe "Fatty" Arbuckle was concurrently establishing himself as a foundational star and director at Keystone Studios. Thus, while his future collaborators were already achieving widespread cinematic fame, Keaton continued to operate as a traditional vaudeville performer. He was largely skeptical of the "flickers" that would eventually facilitate his own stardom.

The family vaudeville act came to a permanent dissolution in early 1917, when Joe Keaton's excessive alcoholism prompted Myra and Buster Keaton to abruptly leave the act in Los Angeles and go to Detroit. Buster Keaton subsequently went to New York to seek independent employment and was soon hired by renowned theatrical agent Max Hart for Shubert Brothers' revue titled The Passing Show. Buster Keaton's transition from the vaudeville stage to cinema was precipitated by a chance encounter on 17th March, 1917 on a New York street. While awaiting rehearsals for The Passing Show, Keaton encountered Lou Anger, a fellow comedian, who introduced him to Roscoe "Fatty" Arbuckle. At this juncture, Arbuckle was a cinematic superstar of global renown, having concluded a prolific tenure at Mack Sennett's Keystone Studios, where he produced an extensive body of work and established himself as an extraordinarily graceful acrobatic comedian, second in popularity only to Charlie Chaplin. Seeking creative autonomy, Arbuckle left Keystone and partnered with producer Joseph M. Schenck, who established the Comique Film Corporation specifically for him. Schenck invested more than $100,000 to equip a Manhattan studio for high quality independent production by Arbuckle.

Upon Arbuckle's invitation, Keaton visited the Comique studio on March 19, 1917. Keaton's creative mind was immediately captivated by the technological intricacies of cinematography and camera mechanics. Keaton recognised a profound vocational calling and disregarded a lucrative $250 per week stage contract for a $40 per week apprenticeship under Arbuckle. Keaton's screen debut in The Butcher Boy established a foundational comic dynamic that immediately distinguished his performance from that of his co-stars, Roscoe Arbuckle and Al St. John. While Roscoe Arbuckle and Al St. John operated within a tradition of high-octane slapstick humour characterised by constant movement and boisterous physical exchanges, Keaton introduced a composed and serious presence to the medium. This stylistic separation is most apparent in the molasses sequence of The Butcher Boy, where Keaton's movements remain purposeful and patient despite the unfolding chaos. It is remarkable that this routine was captured in a single take during Keaton's first visit ever to a film studio.

Following his successful debut, Keaton's professional trajectory in cinema accelerated rapidly. After participating in three initial short films with Roscoe Arbuckle, he assumed the responsibilities of assistant director. By October 1917, Arbuckle's company, the Comique Film Corporation, relocated from New York to Long Beach, California, to utilise more versatile outdoor environments for their increasingly demanding productions. One of the most significant endeavours of this transitional period was A Country Hero, which was the newly formed unit's inaugural production. Balboa Studios constructed a specialised glass facility measuring 100 feet by 200 feet to facilitate this project, which was regarded as the largest of its kind at the time. This film remains the only collaborative work between Arbuckle and Keaton that has not been recovered to date. Their subsequent venture, Out West, required the construction of an entire town set and served as a clever parody of the Western genre popularised by contemporaneous stars such as William S. Hart and Douglas Fairbanks. Keaton's professional momentum was halted after a successful sequence of twelve films when he was drafted into the United States Army in mid-1918. Keaton was deployed to France after being assigned to the 140th Infantry, where his military duties were primarily centered on providing morale-boosting performances for fellow soldiers as part of an entertainment unit known as the Sunshine Players. This task occupied nearly his entire tenure abroad and deferred his return to the film industry until his discharge in 1919.

Producer Joseph Schenck implemented a strategic dissolution of the Keaton-Arbuckle partnership following Keaton's return to Hollywood in 1919 and the completion of his final collaborative shorts, first of which was titled Back Stage. In December 1919, Schenck facilitated Arbuckle's transition to feature-length productions at Paramount to capitalise on the star's immense global popularity and higher earning potential. Consequently, Keaton assumed leadership of the Comique Film Corporation, which was then relocated to Charlie Chaplin's former studio at 1066 Lillian Way and renamed Keaton Studio. Under this new arrangement, Keaton was contracted to produce eight two-reel comedies annually for distribution via Marcus Loew's Metro Pictures. This era of creative autonomy was defined by a prolific partnership with co-director Edward F. Cline, beginning with One Week. It was a nine-minute short parodising a film made by the Ford Motor Company in 1919 titled Home Made. Joseph L. Kelley wrote that "not only is the comedy of the real hilarious brand but without an exception, every incident, every situation is original and presents a front new to the comedy-loving public. (...) Buster is a show in himself and is one of the few eccentric comedians working before the camera who appreciates that the day of the pie-throwing comedy has passed." However, before commencing his independent short series, Keaton debuted as a leading man in the feature film The Saphead. It was a role he secured through the recommendation of Douglas Fairbanks. This pivotal transition effectively ended Keaton's professional apprenticeship and marked his ascent as a primary force in silent cinema.

The prolific collaboration with co-director Edward F. Cline yielded sixteen two-reelers. Notable among these was The Playhouse (1921), a technical marvel where Keaton utilised sophisticated multiple-exposure photography to play every member of a minstrel troupe and its audience at the same time. Another landmark, The Boat, showcased his signature comic gloom as he portrayed a father whose family vessel meets a tragic demise. It is important to note that the precise extent of Edward F. Cline's creative input remains a matter of speculation. Like Roscoe Arbuckle, Keaton was notably generous in sharing credit. He consistently acknowleded his staff as contributors and refused sole billing on all but one of his productions. This modesty often obscured his singular artistic control. Clyde Bruckman, who later joined the studio as a gagman, remarked in Rudi Blesh's biography of Keaton, “You seldom saw his name in the story credits. But I could tell you... that those wonderful stories were ninety percent Buster's. (...) Most of the direction was his, as Edward F. Cline will tell you (...) Comedian, gagman, writer, director—then add technical innovator. He had judgment, taste; he never overdid it and never offended. He knew what was right for him”

While Keaton's professional trajectory reached new heights with feature production, his mentor Roscoe Arbuckle faced a catastrophic collapse. In September 1921, Arbuckle was involved in a scandal following the death of young actress Virginia Rappe during a party in San Francisco. Although he was eventually acquitted after three trials, the public backlash destroyed his career. Keaton remained a steadfast friend, later recalling the trials as a dreadful period that dragged on month after month. He intended to testify on Arbuckle's behalf but was dissuaded by legal counsel who feared that the testimony of prominent Hollywood stars might negatively impact the case. Despite the final acquittal, many observers believed that the verdict had been secured through the influence of industry bigwigs. The outcry caused by the case rendered the production of further films starring Arbuckle professionally unviable. This prompted Joseph Schenck to establish Buster Keaton as the primary star of the organisation. On March 2, 1922, the Comique Film Corporation was formally rebranded as Buster Keaton Productions, Inc. in a strategic effort to distance the studio from Arbuckle's legacy and the controversies associated with the original name. This shift in the industry's collective consciousness is famously characterised by Keaton's own phrase, "The Day the Laughter Stopped." The national uproar triggered by this scandal served as a catalyst for the establishment of the Hays Office. This self-regulating censorship board formulated the restrictive Production Code to avoid external government intervention by monitoring the moral content of American films.

By 1923, Buster Keaton and Joseph Schenck decided to transition away from the short format, having observed the commercial success of feature films by contemporaries like Charlie Chaplin and Harold Lloyd. Keaton's independent directorial feature debut, The Three Ages, parodied D.W. Griffith's Intolerance by juxtaposing romantic rivalries across the Stone Age, ancient Rome and the Prohibition era. Although Keaton later described the film as three two-reelers spliced together, its box-office success proved he could successfully translate his stoic persona and comic precision into a longer narrative structure.

Keaton's earlier shorts were often built around the brilliant spectacle of isolated stunts. However, Our Hospitality represents a more balanced mastery of the feature-film format. Keaton created one of his most significant films which launched a definitive streak of creative success throughout the 1920s. The film is celebrated for its dangerously staged action, particularly a waterfall rescue sequence where the mechanics of the stunt work seem impossible in reality . Our Hospitality held a special place in Keaton's heart because it allowed him to integrate his lifelong passion for railroads, featuring sequences that serve as clear precursors to his later masterpiece, The General. Our Hospitality was shot on location near Lake Tahoe and the Truckee River and the production remains one of his most visually stunning works. It is unique as the only production in which he starred alongside his first wife, Natalie Talmadge, and the only film to feature three generations of Keatons together on screen.

Keaton's films, like those of his contemporary Chaplin, stood in a league of their own, because the narrative itself was not intended to be funny. In fact, the plots of many of the films had a bleak tone. Sherlock Jr. follows a man who fails to achieve his ambition of becoming a detective and must instead remain an ordinary theatre projectionist. When the protagonist seeks to win over his love interest, another man outwits him, persuades others that he has committed theft, and turns the community against him without any substantial proof. Around 17 minutes into the film, Keaton introduces a surrealist device that today's audiences readily recognize: an extended dream sequence. The protagonist falls asleep and enters the movie screen. In this dream state, he transforms from an inept real-world nobody into the brilliant Sherlock Jr. The film can be seen as a meditation on the appeal of cinema and how spectators project themselves into the characters seen on screen to feel their emotions and enjoy their wins as own. Keaton refused to fake his physical feats and often placed his body under extreme stress to achieve the desired effect. An iconic stunt in the film involved Keaton running along the tops of freight cars and grabbing a descending waterspout. The heavy volume of water smashed him against the tracks and actually fractured his neck. Keaton suffered from blinding headaches for months after this accident but continued his work.

Producer Joseph Schenck acquired the screen rights to Roi Cooper Megrue's 1916 stage play Seven Chances without consulting Buster Keaton. Keaton resented this setup because it forced him to adapt a conventional farce that stifled his usual style of comedy. Seven Chances centers on Jimmy Shannon (Buster Keaton), a man who must marry before seven o'clock to claim a million-dollar inheritance. The film begins as a gentle romance and shifts to a comedy of errors. An accidental rock slide during filming and the audience reaction to the test reels inspired Keaton to expand the climax into a spectacularly lethal sequence where  boulders chase him down a hill. The film performed reasonably well commercially, though it fell short of its predecessor, The Navigator. Keaton biographer Tom Dardis attributes this partly to fierce competition from fellow comedians: both Charlie Chaplin's The Gold Rush and Harold Lloyd's The Freshman arrived the same year as Seven Chances. Reviewers noted similarities between Keaton's portrayal of the desperate groom and Lloyd's signature "go-getter" persona. Schenck welcomed these comparisons strategically.  He knew that Lloyd's films consistently outgrossed Keaton's, and calculated that aligning Buster with Lloyd's popular archetype might boost returns. The strategy ultimately failed. Keaton absorbed the borrowed material and transformed it into something distinctly his own.

The ambitious scale of Keaton's next, and arguably one of the greatest films of all time, The General possibly stemmed from two different factors. Keaton's three preceding films, Go West, Seven Chances, and Battling Butler, generated decent profits for Schenck. As a result, he rewarded Keaton with approval for his most expensive production to date. Simultaneously, Schenck became the president of United Artists after sudden death of its founding president Hiram Abrams in early 1926. This position brought new institutional pressures and influences on Schenck. He now operated alongside United Artists' owners, Charlie Chaplin, Mary Pickford, and Douglas Fairbanks, all of whom had a big-budget approach to their productions. This environment almost certainly shaped Schenck's willingness to fund The General on an epic scale. He redirected the film's distribution through United Artists rather than honouring prior commitments with MGM. The result was Keaton's most technically demanding and larger than life film. The General drew directly from an actual Civil War incident, the 1862 Great Locomotive Chase. For this film, he pursued historical authenticity with utmost dedication and extensively researched period details to reconstruct the era with unprecedented realism. Keaton built complex gags around the grand central prop of the film, a locomotive train, and refused to fake even the most dangerous sequences. He spent over forty thousand dollars to crash a real train into an Oregon river in order to achieve authenticity. This commitment to reality produced a masterpiece which audiences, scholars and critics alike now rank among the finest in the history of celluloid.

To the surprise of all modern film fans, The General was a commercial disaster. Keaton biographer Tom Dardis suggests that the film's narrative richness worked against its success at the time. Audiences of the twenties found the film's intricate story and rapid pace difficult to follow. Contemporary critics also published hostile reviews and claimed that the picture lacked enough humour to satisfy traditional comedy fans. Distribution problems also hampered the film's earnings. United Artists failed to market the film with the same intensity and strategic reach that MGM had devoted to Keaton's earlier successes. The studio relied on limited advertising and failed to hire top-tier artists for the promotional campaign. Furthermore, many theatre owners refused to book the film because they resented the high rental prices that United Artists demanded. The failure eventually forced Keaton to abandon his independent status and sign with MGM, a transition he later called the greatest mistake of his life.

The failure of The General prompted Keaton and his financial backers to look for a story that was in vogue. Inspired by the success of films set in college life, such as Wesley Ruggles' The Plastic Age, Jack Conway's Brown of Harvard, Clarence Badger's The Campus Flirt, and most successful of all, Harold Lloyd's The Freshman, Keaton thought that his next film College's setting would be well suited to his style while also providing basis for romance and a natural home to showcase his athletic ability. During its production, Keaton was bereft of his usual crew due to personal and professional reasons and had to bring on a new writer, Carl Harbaugh, and a new director, James W. Horne. He was frustrated with both men on set and later in life revealed that they were of no use to the picture and he had to write and direct the film himself. Generally considered one of the weakest of Keaton's independent features, College was also a commercial flop. The losses were less severe than those incurred on The General, owing to its inexpensive budget. Its commercial disappointment increased the anxiety of Keaton's production company's stockholders, who began to feel that independent production was not the money-making venture they had hoped to be.

Steamboat Bill, Jr. provided the world with the most ubiquitous image associated with Buster Keaton: a man standing motionless while the façade of a building falls on him and is saved only by a strategically placed window opening. He said later of the gag, “We built the window so that I had a clearance of two inches on each shoulder, and the top missed my head by two inches and the bottom my heels by two inches.” In the film, Keaton plays a son who is reunited with his father after many years of separation and must help him save his steamboat business. Much of the comedy flows from the physical disparity between father and son: Torrence's 6-foot-4 frame towers over Keaton's slight physique. In this satire of masculinity, the meek Keaton ultimately saves the principal characters of the picture in a climax featuring one of the most memorable sequences of Keaton's filmography. The tornado sequence was originally conceived as a flood but the aftermath of the Great Mississippi Flood of 1927 made the producers nervous, and they insisted that Keaton change the climax. Joe Keaton's oft-told tale of Buster's childhood, in which he was caught in a violent storm, provided Keaton with inspiration for gags built around the town's destruction by the tornado. Having gone over the initial budget by more than a hundred thousand dollars, the film's production was a tumultuous feat, to say the least. Keaton was informed by Joseph Schenck during production that this would be the last independent venture of Buster Keaton Productions. Wall Street, too, whose financing was essential to bankroll these projects, had grown hostile to independent productions, viewing it as commercially unviable compared to the factory-like efficiency of the major studios. The film was not a huge success at the box-office, though this could scarcely be blamed on audiences' disinterest. It had more to do with United Artists' apathy in securing successful distribution. It was a sign to Keaton that there was little future for him at United Artists.

Near the end of 1927, Keaton found himself at a difficult juncture in his career. From the very beginning, he had been taken under the wing of someone who cared for him and his interests. First Roscoe Arbuckle, and then Joseph Schenck had ensured that Keaton need only concern himself with the artistic side of filmmaking. Unlike his contemporaries Chaplin and Lloyd, who had accumulated enough profit from their films to run their own independent production companies with complete artistic control, Keaton did not even own any shares in the production company named after him. Therefore, it left him particularly vulnerable when Schenck withdrew his financial support. Keaton was uncertain and approached several major studios to negotiate a favourable deal, but in vain. Every studio wanted Buster Keaton the actor, but none were enthusiastic about Keaton the director. His request for an independent unit at Paramount was denied by Adolph Zukor, who already had such an arrangement with the more successful Harold Lloyd. Schenck advised Keaton to join MGM, where his brother Nicholas Schenck was the president, assuring him that his interests would be looked after. MGM, whose roster was dominated by dramatic stars such as Greta Garbo and John Gilbert, was also eager to add a star comedian to its ranks. And so, Keaton relented and signed with MGM but with a contract that afforded him no artistic control. Some of the films he made under the banner of MGM were The Cameraman, Spite Marriage, Free And Easy and Dough Boys.

Keaton's reunion with MGM began with The Cameraman, a film about a small-time tintype photographer in New York City who wants the usual things, success and romance, and the comedy that ensues in his pursuit of them. For The Cameraman, Keaton was able to bring back some of his usual crew, but he was assigned a new director by MGM, Edward Sedgwick, with whom his working relationship grew complicated during shooting. The tension arose on two fronts: Keaton's spontaneous demands to create sequences he considered funny made Sedgwick feel his authority was being undermined, and Sedgwick in turn had to answer to MGM's top brass, who questioned why the film was going over budget and departing from the script. Yet the highlights of the film came from precisely this spontaneous approach. One such sequence had Keaton battling Edward Brophy in a cramped dressing room as they struggled to undress and dress in their swimsuits, with Keaton emerging from the dressing room in a comically ill-fitted swimsuit. The scene ran over four minutes, and Irving Thalberg, MGM's head of production, laughed hysterically while viewing the footage in the rushes. Keaton had, if not total, at least dominant creative control over The Cameraman, and the film was a huge success both critically and commercially. But MGM was not satisfied with the profits the film returned, which was meagre compared to productions starring its famous players such as Lon Chaney and Greta Garbo whose films were cheaper to produce due to MGM's tighter grip on the shooting process and they earned at least twice as much. MGM thus concluded that the only way to make their star comedian worth his salary was to cut the production costs of his films, which meant total adherence to the shooting script and the erosion of whatever artistic control Keaton still retained.

The dawn of sound came in 1927 with Warner Brothers' The Jazz Singer. However, Keaton's studio, MGM, held out against this development the longest before eventually having to relent, and Keaton ventured into the unknown realm of sound films. A myth has persisted that sound was the cause of Keaton's career demise. Nothing could be further from the truth. Keaton's sound films, including the first one, titled Free and Easy fared extremely well commercially, outgrossing every film he had made under Joseph Schenck. But it was precisely this commercial success that eroded his bargaining power with the studio, and his objections to the scripts assigned to him fell on deaf ears. Keaton did not resist the coming of sound per se, but he was deeply unhappy about the primitive techniques of early sound films, which forced characters to talk incessantly at the expense of physical comedy. No longer in a position to concoct his own scripts, construct his own sets and contraptions, or choose his own locations, Keaton allowed himself to be cast against type as an inept bumpkin in a series of thoroughly forgettable features. With each successive picture, budgets were cut further, and profits soared. "Keaton" had become a standardised product at MGM. Diminished and stripped of creative agency, he increasingly turned to alcohol, which began to take control of his life. It could be seen by contemporaries on his face, in his professional behaviour, and on set, where lethargy became a common occurrence.

Louis B. Mayer terminated Keaton's contract in February 1933 after the actor missed production days during the filming of What! No Beer?. Irving Thalberg could not intervene because he was recovering from a heart attack at the time. Keaton subsequently moved to Paris in 1934 to star in Le Roi des Champs-Élysées for Nero Films. This production had a script that accommodated Keaton's preference for visual storytelling over heavy dialogue. Upon returning to the United States, Keaton signed with Educational Pictures to produce sixteen shoestring-budget two-reelers. While many of these shorts were formulaic, he earned a co-writing credit on the 1936 film Grand Slam Opera. After Educational closed its Hollywood office in 1937, Keaton returned to MGM as a gag writer for $200 a week. He supplied routines for various stars and contributed to some of the Marx Brothers' productions, including their classic At the Circus. In 1939, Columbia Pictures hired Keaton to star in ten two-reelers for twenty-five hundred dollars per film. These shorts often relied on older material but provided him with steady work during a period of professional decline.

On May 29, 1940, Keaton married Eleanor Norris. She was a dancer under contract with MGM. Eleanor played a key role in steadying Keaton's life by managing his household and finances as his life was spiraling downward. Following the marriage, Keaton moved from producing two-reelers back to writing gags for stars like Richard Bernard Skelton (Red Skelton). A academic 1949 essay by James Agee titled Comedy's Greatest Era initiated a massive resurgence of interest in Keaton's early masterpieces. Agee's essay highlighted Keaton's films for their formal precision, intelligence and emotional understatement and contributed to the later canonisation of his films within academic disciplines and as well as public. This renewed interest in his work made way for Keaton to work in notable supporting roles in major productions such as In the Good Old Summertime, Sunset Boulevard, and Around the World in 80 Days. In 1952, Charlie Chaplin hired him for a significant performance sequence in Limelight. Keaton also investigated the new medium of television during this era. He launched his own live series on KTTV in 1951 but eventually canceled it due to the stress of creating new routines weekly.

In the year 1954, Keaton met Raymond Rohauer, a young film collector who preserved Keaton's films from deterioration. He recognised Keaton at his theatre in 1954 and asked about the actor's surviving collection. Rohauer moved these films from highly inflammable nitrate stock onto safer cellulose acetate. He also navigated complex legal channels to acquire the rights to the material from the surviving trustee of Keaton's production company. This preservation effort triggered a massive global resurgence of interest in Keaton's films. Raymond Rohauer later built a massive collection of silent movies that is now popularly known as Rohauer Library. He used cunning strategies to secure the rights to these films and tightly controlled their distribution. His licensing methods and business tactics made him a notorious figure among his contemporaries. Although he rescued many films from physical decay, his peers often disputed his unethical methods for acquiring and maintaining the library. Owing to the restoration, there was a huge resurgence in Keaton's work. Additionally, actor James Mason discovered a cache of high quality prints within Keaton's former residence. Buster Keaton was portrayed by actor Donald O'Connor in his biopic titled The Buster Keaton Story in 1957. He was honoured with a lifetime achievement award at the 32nd Academy Awards in 1959.

Keaton published his autobiography, My Wonderful World of Slapstick in 1960 with the assistance of writer Charles Samuels. He accepted various character roles starting in 1964, including some productions for American International Pictures. In 1965, he collaborated with Gerald Potterton on The Railrodder and Samuel Beckett on the experimental project Film. This minimalist, philosophical production with no sound features Keaton as a man desperately attempting to avoid all forms of observation. Keaton infuses the film with a sense of eeriness and marks the medium with one last formal experiment. Keaton succumbed to lung cancer on February 1, 1966, shortly after his official diagnosis. He left behind his wife Eleanor, two sons, and multiple grandchildren.