After graduating from high school, Mostel enrolled in the City College of New York. This was followed by a year at New York University.
In 1937 Mostel joined the Federal Art Project (part of the Works Projects Administration) and taught art at the 92nd Street Young Men and Young Women's Hebrew Association. He also gave lectures at various museums. Mostel talks were very humourous and he was soon being invited to perform at private parties and local clubs. It was during this period that a press agent at one of the clubs gave him the nickname Zero because he was a "guy who's started from nothing".
After the war Mostel continued to work as a standup comedian in nightclubs. He also started acting and appeared in the film Panic in the Streets in 1950. This was followed by Sirocco (1951), The Guy Who Came Back (1951), The Enforcer (1951) and The Model and the Marriage Broker (1951).
Mostel held left-wing political views and when the House of Un-American Activities Committee (HUAC) began an investigation into the Hollywood Motion Picture Industry it was not long before he was called to give evidence. Mostel denied he was a member of the Communist Party but he refused to provide information about the political opinions of his friends.
Mostel was now blacklisted and this made it very difficult for him to work in the entertainment industry. Around 320 artists, including Larry Adler, Stella Adler, Leonard Bernstein, Marc Blitzstein, Joseph Bromberg, Charlie Chaplin, Aaron Copland, Hanns Eisler, Edwin Rolfe, Carl Foreman, John Garfield, Howard Da Silva, Dashiell Hammett, E. Y. Harburg, Lillian Hellman, Burl Ives, Arthur Miller, Dorothy Parker, Philip Loeb, Joseph Losey, Anne Revere, Pete Seeger, Gale Sondergaard, Louis Untermeyer, Josh White, Clifford Odets, Michael Wilson, Paul Jarrico, Jeff Corey, John Randolph, Canada Lee, Orson Welles, Paul Green, Sidney Kingsley, Paul Robeson, Richard Wright and Abraham Polonsky, were also blacklisted.
For the next few years Mostel found it difficult to find work in clubs and theatres and had to supplement his income by trying to sell his paintings. In 1958 a friend managed to get him the part of Leopold Bloom in the Off-Broadway production of Ulysses. He was a great success and won an Obie.
With the blacklist over Mostel returned to work in TV. In January 1960 Mostel was involved in a serious road accident and spent over five months in hospital. After his recovery he appeared in several hit Broadway shows including Rhinoceros, A Funny Thing Happened on the Way to the Forum and Fiddler on the Roof.
Mostel also appeared in the films A Funny Thing Happened on the Way to the Forum (1966), The Producers (1968), The Great Bank Robbery (1969), Rhinoceros (1973), Once Upon a Scoundrel (1973) and Journey Into Fear (1975). In 1976 Mostel appeared in The Front, a film about the Hollywood Blacklist. Zero Mostel died of a heart-attack on 8th September 1977.