 | Bob Hoskins als Eddie Valiant |
 | Christopher Lloyd als Judge Doom |
 | Joanna Cassidy als Dolores |
 | Charles Fleischer als Roger Rabbit / Benny The Cab / Greasy / Psycho (voice) |
 | Stubby Kaye als Marvin Acme |
 | Alan Tilvern als R.K. Maroon |
 | Richard LeParmentier als Lt. Santino |
 | Lou Hirsch als Baby Herman (voice) |
 | Betsy Brantley als Jessica's Performance Model |
 | Joel Silver als Raoul |
 | Paul Springer als Augie |
 | Richard Ridings als Angelo |
| Edwin Craig als Arthritic Cowboy |
| Lindsay Holiday als Soldier |
 | Mike Edmonds als Stretch |
 | Morgan Deare als Editor / Gorilla (voice) |
| Danny Capri als Kid #1 |
| Christopher Hollosy als Kid #2 |
| Jean-Paul Sipla als Kid #3 |
| Laura Frances als Blonde Starlet |
| Joel Cutrara als Forensic #1 |
 | Billy J. Mitchell als Forensic #2 |
| Eric B. Sindon als Mailman |
 | Ed Herlihy als Newscaster |
 | James O'Connell als Conductor |
| Eugene Gutierrez als Teddy Valiant |
 | April Winchell als Mrs. Herman (voice) |
 | Mae Questel als Betty Boop (voice) |
 | Mel Blanc als Bugs Bunny/Daffy Duck/Tweety Bird (voice) |
 | Tony Anselmo als Donald Duck (voice) |
| Mary T. Radford als Hippo (voice) |
 | Joe Alaskey als Yosemite Sam / Foghorn Leghorn (voice) |
 | David L. Lander als Smart Ass (voice) |
 | Fred Newman als Stupid (voice) |
 | June Foray als Wheezy/Lena Hyena (voice) |
 | Russi Taylor als Birds / Minnie Mouse (voice) |
| Les Perkins als Mr. Toad (voice) |
 | Richard Williams als Droopy (voice) |
 | Wayne Allwine als Mickey Mouse (voice) |
 | Pat Buttram als Bullet #1 |
 | Jim Cummings als Bullet #2 |
 | Jim Gallant als Bullet #3 |
 | Frank Sinatra als Singing Sword (voice) (archive sound) |
 | Tony Pope als Goofy / Big Bad Wolf (voice) |
| Peter Westy als Pinocchio (voice) |
 | Cherry Davis als Woody Woodpecker |
 | Jack Angel als Additional Voices (voice) (uncredited) |
| Jeff Arbaugh als Mime (uncredited) |
 | Corey Burton als Judge Doom (high-pitched voice) (voice) (uncredited) |
 | Nancy Cartwright als Dipped Shoe (voice) (uncredited) |
 | Amy Irving als Jessica Rabbit (singing voice) (uncredited) |
 | Mickie McGowan als Mooing Cow / Flying Witch (voice) (uncredited) |
 | Kathleen Turner als Jessica Rabbit (voice) (uncredited) |
 | Frank Welker als Dumbo (voice) (uncredited) |
| Alan Silvestri | Original Music Composer |
| Robert Zemeckis | Director |
| Steve Starkey | Associate Producer |
| Arthur Schmidt | Editor |
| Steven Spielberg | Executive Producer |
| Kathleen Kennedy | Executive Producer |
| Joanna Johnston | Costume Design |
| Frank Marshall | Producer |
| Robert Watts | Producer |
| Elliot Scott | Production Design |
| Dean Cundey | Director of Photography |
| Roy Barnes | Set Designer |
| Philip Kohler | Location Manager |
| Charles L. Campbell | Supervising Sound Editor |
| Charles Croughwell | Stunts |
| George Gibbs | Special Effects Supervisor |
| Peter Robb-King | Makeup Artist |
| Stephen Scott | Art Direction |
| Robert R. Benton | Set Decoration |
| Rocky Taylor | Stunts |
| Jeffrey Price | Screenplay |
| Peter S. Seaman | Screenplay |
| Gary K. Wolf | Novel |
| Don Hahn | Associate Producer |
| Roger Cain | Production Design |
| Ken Chase | Key Makeup Artist |
| Brian Smrz | Stunts |
| Simon Wells | Supervising Animator |
| Ken Ralston | Visual Effects Supervisor |
| Bob Yerkes | Stunts |
| Robert Stevenhagen | Animation |
| Phil Nibbelink | Supervising Animator |
| Andreas Deja | Supervising Animator |
| Colin Jamison | Hairdresser |
| Michael Lantieri | Special Effects Supervisor |
| Richard Williams | Animation Director |
| Andy Bradford | Stunts |
| Vera Pacheco | Animation |
| Martin Cohen | Post Production Supervisor |
| Vincent Keane | Stunts |
| Terry Jackson | Stunts |
| William McAllister | Art Direction |
| Frank Tudisco | Script Supervisor |
| Stuart Fell | Stunts |
| Terry Walsh | Stunts |
| Reg Harding | Stunts |
| Peter Howitt | Set Decoration |
| Louis L. Edemann | Supervising Sound Editor |
| Kenneth Karman | Music Editor |
| Tony Dawe | Sound Mixer |
| Chris Brock | Second Assistant Director |
| Wes Takahashi | Animation Supervisor |
| Gregg Smrz | Stunts |
| Silvia Pompei | Animation Manager |
| Claire Williams | Animation Manager |
| James Baxter | Animation |
| Pat Sito | Animation Manager |
| Frans Vischer | Animation |
| Jason White | Stunts |
| Larry Singer | ADR Supervisor |
| Bill Kimberlin | Visual Effects Editor |
| Lynn Christopher | Set Designer |
| Daniel O'Haco | Stunts |
| Linda Henrikson | Costume Supervisor |
| Uli Meyer | Animation |
| Sharleen Rassi | Key Hairdresser |
| Alan L. Nineberg | ADR Editor |
| Jane Royle | Prosthetic Makeup Artist |
| Del Baker | Stunts |
| Suella Kennedy | Visual Effects Coordinator |
| Russell Hall | Supervising Animator |
| Fred Haggerty | Stunts |
| Daniel K. Moore | Stunts |
| Christopher Knott | Animation Supervisor |
| Ed Jones | Visual Effects |
| Peter Western | Animation |
