In the early 1980s, Buscemi worked as a firefighter for four years on FDNY Engine 55. After 9/11, Buscemi returned to Engine 55 and worked alongside other firefighters to go through the rubble from the World Trade Center. Buscemi later narrated the documentary Dust to Dust: The Health Effects of 9/11.
An associate member of the renowned experimental theater company The Wooster Group, Buscemi is known for playing the "Buddy Holly" waiter in Quentin Tarantino's Pulp Fiction, Mr. Pink in Reservoir Dogs, Donny in The Big Lebowski, Romero in Spy Kids 2 and Spy Kids 3D, Wesley in Home on the Range, Horace Nebbercracker in Monster House (voice and motion-capture), Templeton in Charlotte's Web, and Bucky in G-Force.
He also starred as Tony Blundetto in The Sopranos and currently stars as Enoch "Nucky" Thompson in Boardwalk Empire, both HBO television series, the latter of which earned him a Screen Actors Guild Award, a Golden Globe and a nomination for an Emmy Award in 2011.