A native of New York City, Jackson began his career as a child actor in Broadway productions at the age of twelve, in the production The Ragged Earl, which had a short run at the Academy of Music in 1899. He appeared in several more productions as a youth over the next four years, before taking a ten-year absence from the stage. He returned to the theater in 1913, where he remained until the end of the 1920s, appearing in or producing a dozen plays.

His last stage performance was in the hit play Broadway, directed by George Abbott and Philip Dunning, which ran from 1926–28 at the Broadhurst Theatre. Jackson’s portrayal of the sarcastic detective Dan McCorn earned him an invitation to reprise the role the following year in the film version of the play. Although he had appeared in minor roles in two 1910s films which had been produced in New Jersey (where the film industry was largely located prior to its move west), this was his first featured role. He returned only once more to Broadway, in the role of producer, for the successful 1928 play Gentlemen of the Press. The success of his performance reprising his role of Detective McCorn in Universal’s 1929 film Broadway started Jackson’s lengthy 38-year career in film and television. He followed up this initial success with several performances in 1930, and in 1931 with a notable performance in Little Caesar, starring Edward G. Robinson, again in the role of the sarcastic police officer.

One of his more noticeable roles was playing Richard Snow in the hit drama Manhattan Melodrama. Most of the roles throughout his career were smaller character roles, with occasional featured roles, as in 1935’s The Call of the Wild, thrown in. Notable films in which he appeared included The Thin Man (1934); Angels With Dirty Faces (1938); Beau Geste (1939), Yankee Doodle Dandy (1942),Union Station (1950); and Stars and Stripes Forever (1952). He also appeared in the original 1945 version of the classic film noir The Big Sleep (1946), but his on-screen time was cut out when changes were made to it before its ultimate release in 1946. His part (along with the part played by actor James Flavin in the same scene) was eventually seen by the general audience when the original version was released in the 1990s. His final film role, a year before his death, was an uncredited bit as a minister in 1966’s A Big Hand for the Little Lady.

Jackson began appearing in episodic television in 1954. He appeared in guest spots on dozens of television shows, such as Dragnet, Adventures of Superman, Have Gun – Will Travel, and 77 Sunset Strip. His last appearance was also in 1966, playing the Governor in an episode of the NBC sitcom, Camp Runamuck.