He performed in the circus, burlesque, vaudeville, and the legitimate theatre before joining Biograph studios in 1909 as an actor. He soon became a scriptwriter and director, learning movie technique from D.W. Griffith, a director who pioneered in the development of cinematic art. Three years later he left to form his own independent Keystone Company in Los Angeles.

In 1914 Sennett's company produced the first American feature-length comedy, Tillie's Punctured Romance, but he is most famous for more than 1,000 one- and two-reel comedy shorts. At first he both directed and acted in his short comedies, many of which were improvised on the spot to take advantage of parades, fires, and similar events too costly to stage. His name is generally associated with the bathing beauties who adorned his comedies and with the antics of the Keystone Kops, a group of uniquely talented actors who became internationally popular comedians. The vintage Sennett films, however, such as His Bitter Pill (1916), A Small Town Idol (1921), and The Shriek of Araby (1923) were often biting parodies or incisive satires that mocked the foibles of an increasingly mechanized society. His films were characterized by trick camera work and high-speed and slow-motion photography reminiscent of the French “chase” comedies popular in the United States after 1907.

The coming of sound, the advent of double features, and the popularity of animated cartoons, combined with the Wall Street crash of 1929 that wiped out his large personal fortune, severely crippled Sennett's style, and he retired in 1935. In 1937 the Academy of Motion Picture Arts and Sciences voted him a special award “for his lasting contribution to the comedy technique of the screen.”