Buscemi is an associate member of the experimental theater company The Wooster Group. Buscemi’s first appearance was in Parting Glances in 1986, where he played Nick, an AIDS stricken man.

He first hit the cinema in 1988 film Call Me, where he played Switchblade. He also was in Tales from the Darkside, a 1990 film with 3 segments, where Buscemi starred in the first, playing Bellingham, a college student who orders a mummy and unleashes it on fellow college students played by Christian Slater and Julianne Moore.

During 1990, Buscemi had a couple of additional crime roles. He played the henchman of Laurence Fishburne named Test Tube in Christopher Walken’s King of New York, and played Mink in the Coen Brothers Millers Crossing. This marked the first of six films of the Coen Brothers which Buscemi appeared in.

In 1991 he played the bellboy, Chet, in the Coen Brothers film, Barton Fink. His first lead role was in 1992, where he played Adolpho Rollo in In the Soup.