Comden studied dramatics at New York University (B.S., 1938). Green attended New York public schools and, during the Great Depression, found his first job as a Wall Street runner. Comden and Green met in 1938 while both were making the rounds of theatrical agents. The Village Vanguard, a bohemian nightclub in Greenwich Village, was seeking a new show; and the group that became known as The Revuers stepped in—Comden, Green, Judy Tuvim (Holliday, Judy), Alvin Hammer, and John Frank. Their satirical show of songs, dances, and skits enjoyed initial success and went from the Vanguard to engagements at uptown theatres and nightclubs and on radio but flopped in Hollywood. (Judy Tuvim stayed on in Hollywood and, except for occasional returns to Broadway, became, as Judy Holliday (Holliday, Judy), one of the most brilliant film comediennes of the 1950s.)

In 1944, back in New York, Comden and Green joined with composer Leonard Bernstein (Bernstein, Leonard) and choreographer Jerome Robbins (Robbins, Jerome) in creating the musical On the Town, which later (1949) was filmed by MGM. In 1951, with Two on the Aisle, Comden and Green began their long collaboration with composer Jule Styne, who created the music for most of their shows, including Peter Pan (1954), Bells Are Ringing (1956), Say, Darling (1958), Do Re Mi (1960), Subways Are for Sleeping (1961), Fade Out–Fade In (1964), Hallelujah, Baby! (1967), and Lorelei (1974).

Comden and Green wrote another musical with Bernstein, Wonderful Town (1953), which won them their first Tony Award; they won six others, for Hallelujah, Baby!, Applause (1970), On the Twentieth Century (1978), and The Will Rogers Follies (1991). They also wrote several film scripts, including that of Auntie Mame (1958) and Singin' in the Rain (1952), the latter of which was voted the best film musical of all time by the American Film Institute. Among their best-known songs are "Just in Time" and "The Party's Over." In 1980 Comden and Green were named to the Songwriters Hall of Fame. Comden's memoirs, Off Stage, were published in 1995.