John Bunny attended High School in Brooklyn and worked as a grocery clerk before joining a small minstrel show touring the East Coast. He went on to jobs as stage manager for various stock companies and performed in vaudeville before being drawn to the fledgling motion picture business. By 1910, Bunny was working at Vitagraph Studios where the happy-go-lucky, rotund man quickly became an international star of silent film comedies. At Vitagraph he starred in a series of over 100 wildly popular comedies with the comedian Flora Finch that were popularly called Bunnyfinches.

John Bunny had only been acting in films for five years when he died from Bright's disease and was interred in the Cemetery of the Evergreens in Brooklyn, New York. Because silent film had no language barrier, Bunny's popularity was such that his death was front-page news in Europe as well as the United States.

Following his passing, advances in technology and in stunts brought great new comedic stars to silent film that relegated John Bunny to the status of an almost completely-forgotten actor. However, John Bunny was eventually honored for his contribution to the motion picture industry with a star on the Hollywood Walk of Fame at 1715 Vine Street in Hollywood.