Buscemi has appeared in independent and mainstream films including Living in Oblivion (1995), Desperado (1995), Con Air (1997), Armageddon (1998), Ghost World (2001), Big Fish (2003), and The Death of Stalin (2017).

He also appeared in supporting or cameo roles in many films with Adam Sandler including Airheads (1994), Billy Madison (1995), The Wedding Singer (1998), Mr.

Deeds (2002), and Hubie Halloween (2020); and provided voice acting roles in the animated films Monsters, Inc. (2001), The Boss Baby (2017), and Transformers One (2024).

Buscemi has also had an extensive career in television, notably starring in the lead role of Enoch "Nucky" Thompson in the HBO series Boardwalk Empire (2010–2014).

(Buscemi's 1996 film Trees Lounge, in which he starred and served as screenwriter and director, is set in and was largely shot in his childhood village of Valley Stream).

[12] Buscemi briefly attended Nassau Community College before moving to Manhattan to enroll in the Lee Strasberg Institute.

[13] Prominent solo performances were given in John Jesurun's Chang in a Void Moon series, as well as appearing in an adaptation of William Shakespeare's play Titus Andronicus, directed by Kęstutis Nakas.

[15] In 1989, he appeared in four films, including James Ivory's comedy Slaves of New York, Howard Brookner's ensemble period film Bloodhounds of Broadway and the New York Stories segment directed by Martin Scorsese entitled, "Life Lessons" starring alongside Nick Nolte and Rosanna Arquette.

[17] In 1990, he played Mink Larouie in the Coen Brothers' neo-noir gangster film Millers Crossing starring opposite Gabriel Byrne, Marcia Gay Harden, and John Turturro.

In 1995, Buscemi guest-starred as suspected murderer Gordon Pratt in "End Game", an episode of the television series Homicide: Life on the Street.

[29] In 1995 he also starred alongside Tarantino and Antonio Banderas in Desperado, and played the lead role in the independent satire film Living in Oblivion.

Subsequently, he gained a reputation as character actor,[31] with supporting roles in blockbuster action films: as Garland Greene in Simon West's Con Air (1997) and Rockhound in Michael Bay's Armageddon (1998).

Buscemi also appeared as Donny in the Coen's cult classic black comedy film The Big Lebowski (1998) starring Jeff Bridges and John Goodman.

During this time he also made his directing debut the episode: "Finnegan's Wake" (1998) of the NBC drama Homicide: Life on the Street.

[33] Buscemi received numerous nominations for his performance including for the Golden Globe Award for Best Supporting Actor – Motion Picture.

Buscemi's performance garnered him a Golden Globe Award for Best Actor – Television Series Drama;[40] he later received two more nominations for his work on the same show.

He hosts, directs, and produces his own web series talk show, Park Bench with Steve Buscemi, which ran from 2014 to 2015.

[48] In 2016, Buscemi acted in the political drama Norman: The Moderate Rise and Tragic Fall of a New York Fixer starring Richard Gere.

The following year he starred as Del Montgomery in the British coming of age drama Lean on Pete (2017) directed by Andrew Haigh.

During this time Buscemi continued taking roles in comedy films such as The Week Of (2018), The Dead Don't Die (2019), The King of Staten Island (2020), and Hubie Halloween (2020) as well as voicing roles in The Boss Baby (2017), Transformers: The Last Knight (2017), Hotel Transylvania 3: Summer Vacation (2018), and Hotel Transylvania: Transformania (2022).

In February 2020, Buscemi was cast as Chebutykin in a New York Theatre Workshop revival of Anton Chekhov's Three Sisters alongside Greta Gerwig, Oscar Isaac, and Chris Messina.

His directorial credits include: In addition to feature films, he directed episodes of the television shows Love, Homicide: Life on the Street, The Sopranos, Oz, 30 Rock, Portlandia, and Nurse Jackie.

While scouting a location for a film, Buscemi visited the Philadelphia Eastern State Penitentiary and found the building so interesting that he later provided the majority of the narration for the audio tour there.

Playing against his image, during a flashback he appears to be disguised as a teenager as he says that he was "part of a special task force of very young-looking cops who infiltrated high schools".

[62] Buscemi was stabbed multiple times in April 2001 at the Firebelly Lounge in Wilmington, North Carolina, while shooting the film Domestic Disturbance.

[65] He also has a post-credit scene in the Spike Jonze–directed documentary Beastie Boys Story in which he pokes fun at the commercial failure of the group's second studio album, Paul's Boutique; "When the tree fell in the forest, nobody heard that shit," jokes Buscemi.

The day after the September 11 attacks in New York, he returned to his old firehouse to volunteer; he worked twelve-hour shifts for a week, digging through rubble to search for missing firefighters.

[75] In 2021, Buscemi spoke to podcast host Marc Maron[76] about his issues with PTSD, a consequence of the five days he spent volunteering in the aftermath of 9/11.

He also received five Independent Spirit Award nominations, winning twice for Best Supporting Male for his roles in Reservoir Dogs (1992) and Ghost World (2003).

In 2014, Buscemi was named Honorary battalion chief by the New York City Fire Department after his early career serving as a fireman, and for his return to the service during 9/11.