Om te infiltreren in de New Yorkse maffia neemt FBI undercover agent Joe Pistone (Johnny Depp) de identiteit aan van gangster en juwelendief Donnie Brasco. Om sneller tot de hechte maffiastructuur door te dringen, sluit hij vriendschap met Lefty Rugiero (Al Pacino), een cynische oudere huurmoordenaar. Als Lefty's beschermeling stijgt Donnie hoger en hoger in de hièrarchie van de maffia. Donnie begint in te zien dat hij niet alleen de lijn tussen FBI agent en crimineel overschrijdt, maar ook dat hij zijn vriend Lefty bijna zeker de doodstraf zal bezorgen wanneer hij als FBI agent in actie zal komen. Heen en weer geslingerd tussen zijn familie, de FBI en zijn ongewenste, maar oprechte vriendschap met Lefty, wordt het uiterste gevergd van Joe Pistone's alias Donnie Brasco's loyaliteit.
| Al Pacino | Benjamin 'Lefty' Ruggiero |
| Johnny Depp | Donnie Brasco |
| Michael Madsen | Sonny Black |
| Bruno Kirby | Nicky |
| James Russo | Paulie |
| Anne Heche | Maggie Pistone |
| Zeljko Ivanek | Tim Curley |
| eljko Ivanek | Tim Curley |
| Gerry Becker | Agent Dean Blandford FBI |
| Robert Miano | Sonny Red |
| Brian Tarantina | Bruno |
| Rocco Sisto | Richard 'Richie' Gazzo |
| Zach Grenier | Dr. Berger |
| Walt MacPherson | Sheriff |
| Ronnie Farer | Annette Ruggiero |
| Terry Serpico | Strip Club Owner |
| Gretchen Mol | Sonny's Girlfriend |
| Tony Lip | Philly Lucky |
| George Angelica | Big Trin |
| Val Avery | Trafficante |
| Madison Arnold | Jilly |
| Delanie Fitzpatrick | Daughter Amanda Pistone |
| Katie Sagona | Daughter Jessica Pistone |
| Sara Gold | Daughter |
| Larry Romano | Tommy Ruggiero |
| Tim Blake Nelson | FBI Technician |
| Paul Giamatti | FBI Technician |
| James Michael McCauley | FBI Agent |
| Jim Bulleit | U.S. Attorney |
| James Bulleit | U.S. Attorney (as Jim Bulleit) |
| Andrew Parks | U.S. Attorney Hollman |
| Keenan Shimizu | Japanese Maitre D' |
| Rocco Musacchia | Trafficante's Man |
| Joe Francis | Trafficante's Man |
| Sal Jenco | Mare Chiaro Bartender |
| Billy Capucilli | Communion Party Man |
| Laura Cahill | Communion Party Woman |
| Doreen Murphy | Mob Girlfriend |
| Elle Alexander | Mob Girlfriend |
| Denise Faye | Mob Girlfriend |
| Elaine del Valle | Mob Girlfriend (as Elaine Del Valle) |
| John Horton | FBI Director |
| Dan Brennan | FBI Photographer |
| LaJuan Carter | Singer |
| Sandy Barber | Singer |
| Joyce Stovall | Singer |
| Frank Pesce | Wiseguy |
| Randy Jurgensen | Wiseguy |
| John Di Benedetto | Wiseguy (as John DiBenedetto) |
| John DiBenedetto | Wiseguy |
| Richard Zavaglia | Wiseguy |
| Tony Ray Rossi | Wiseguy |
| Edward Black | Wiseguy |
| Gaetano LoGiudice | Wiseguy |
| Carmelo Musacchia | Wiseguy |
| Pat Vecchio | Wiseguy |
| Caleb | The Lion |
| Garry Pastore | Carmine Galante's Bodyguard |
| Peter Sova | Cinematographer |
| Jim Lavin | Arresting FBI Officer |
| Jefferson Sage | Art Director |
| Patrick McCormick | Executive Producer |
| Alan Greenspan | Executive Producer |
| Jon Gregory | Film Editor |
| Patrick Doyle | Composer |
| Tod A. Maitland | production sound mixer |
| Ian Fuller | Supervising Sound Editor |
| Dean Humphreys | Sound Re-Recording Mixer |
| Tim Cavagin | Sound Re-Recording Mixer |
| Aude Bronson-Howard | Costume Designer |
| David Robinson | Costume Designer |
| Donald Graham Burt | Production Designer |
| David C. Robinson | Costume Designer |
| John Caglione, Jr. | Make-Up Artist |
| Margot Boccia | Make-Up Artist |
| Ronald Ottesen, Jr. | Visual Effects |
| David Dumais | Costume Designer |
| Susan J. Wright | Costume Designer |
