Tucci made his Broadway debut in The Queen and the Rebels on 30 September 1982. His film debut was in Prizzi's Honor (1985). Tucci is known for his work in films such as Kiss of Death, Road to Perdition, and Big Night, and in the television series Murder One as the mysterious Richard Cross. Big Night (1996), which he co-wrote with his cousin Joseph Tropiano, starred in, and co-directed with Campbell Scott, premiered at the Sundance Film Festival. The film also featured his sister Christine and mother, who wrote a cookbook for the film. It won him and Tropiano the Independent Spirit Award for Best First Screenplay.
He has been nominated twice for Golden Globes, and won both times for his title role in Winchell (1998), and for his supporting role as Adolph Eichmann in Conspiracy (2001), both for HBO films. He also received a Screen Actors Guild Award nomination for Winchell. He was nominated for Broadway's Tony Award as Best Actor in a Play for his role as Johnny in the 2002 revival