He is known for his varied roles in independent films, and has worked frequently with the Coen brothers, Adam Sandler, and Spike Lee.

He also starred in Coens' Miller's Crossing (1990), Barton Fink (1991), for which he won the Cannes Film Festival Award for Best Actor, The Big Lebowski (1998), and O Brother, Where Art Thou?

He also starred in Fearless (1993), Quiz Show (1994), and Gloria Bell (2018); and portrayed Seymour Simmons in the Transformers film series (2007–2017) and Carmine Falcone in The Batman (2022).

For his guest role in the USA Network comedy series Monk, Turturro received a Primetime Emmy Award.

His mother was born in the U.S. to parents with roots in Sicily, and was an amateur jazz singer who had worked in a naval yard during World War II.

[5] His father had emigrated at age six from Giovinazzo, Italy to the United States, and later worked as a carpenter and construction worker before joining the U.S. Navy.

[7] He created the title role of John Patrick Shanley's Danny and the Deep Blue Sea at the Playwrights Conference at the Eugene O'Neill Theatre Center in 1983.

Turturro had a notable supporting role in William Friedkin's action film To Live and Die in L.A. (1985), as the henchman of the villainous counterfeiter played by Willem Dafoe.

This movie was the first of a long-standing collaboration between the director and Turturro, which includes work together on a total of nine films—more than any other actor in the Lee oeuvre[8]—including Mo' Better Blues (1990), Jungle Fever (1991), Clockers (1995), Girl 6 (1996), He Got Game (1998), Summer of Sam (1999), She Hate Me (2004), and Miracle at St. Anna (2008).

In 2006 he appeared in Robert De Niro's The Good Shepherd, and as the Sector 7 agent Seymour Simmons in four films of the Transformers live-action series.