| Jake Gyllenhaal (Robert Graysmith) |
| Mark Ruffalo (L'inspecteur David Toschi) |
| Anthony Edwards (L'inspecteur William Armstrong) |
| Robert Downey Jr. (Paul Avery) |
| Brian Cox (Melvin Belli) |
| John Carroll Lynch (Arthur Leigh Allen) |
| Chloë Sevigny (Melanie) |
| Ed Setrakian (Al Hyman) |
| Richmond Arquette (Zodiac 1 / Zodiac 2) |
| Bob Stephenson (Zodiac 3) |
| John Lacy (Zodiac 4) |
| John Getz (Templeton Peck) |
| John Terry (Charles Thieriot) |
| Candy Clark (Carol Fisher) |
| Elias Koteas (Le sgt. Jack Mulanax) |
| Dermot Mulroney (Le capitaine Marty Lee) |
| Donal Logue (Le capitaine Ken Narlow) |
| June Raphael (Mme. Toschi) |
| Ciara Hughes (Darlene Ferrin) |
| Lee Norris (Mike Mageau jeune) |
| Patrick Scott Lewis (Bryan Hartnell) |
| Pell James (Cecilia Shepard) |
| Philip Baker Hall (Sherwood Morrill) |
| David Lee Smith (Le père) |
| Jason Wiles (Le technicien Dagitz) |
| Charles Schneider (Cabbie / Paul Stine) |
| James Carraway (Shorty) |
| Tom Verica (Jim Dunbar) |
| Jimmi Simpson (Mike Mageau) |
| Doan Ly |
| Karina Logue (Une femme) |
| Joel Bissonnette (L'inspecteur Kracke) |
| Zach Grenier (Mel Nicolai) |
| John Mahon |
| Matt Winston (John Allen) |
| Jules Bruff (Catherine Allen) |
| John Ennis (Terry Pascoe) |
| J. Patrick McCormack) |
| Adam Goldberg (Duffy Jennings) |
| James Le Gros (L'officier George Bawart) |
| Charles Fleischer (Bob Vaughn) |
| Clea Duvall (Linda del Buono) |
| Paul Schulze (Sandy Panzarella) |
| Adam Trese (Le détective 1) |
| Penny Wallace (La secrétaire de Mulanax) |
| John Hemphill (Donald Cheney) |
| Michel Francoeur |
| Thomas Kopache |
| Giovanna Spuria (La victime) |
| Barry Livingston |
| Christopher Fields |
| Stanley B. Herman |
| Hayati Akbas |
| Martin Andris |
| David Winston Barge |
| Marlo Bernier (Le détective 2) |
| Felix J. Boyle |
| Geoff Callan |
| Brad Carr |
| Cabran E. Chamberlain |
| Cookie Crawford |
| JD Cullum |
| Rod Damer |
| Francois Dominick |
| Judith Drake (Florence Douglas) |
| Carter Evans |
| Mark Falvo (Un reporter) |
| Mitchell Fink (Un reporter) |
| Erica Ford |
| Ted Garcia |
| Gloria Grant (Bettye Harden) |
| Benjamin Hartnell |
| Bryan C. Hartnell |
| Jonathan Hartnell |
| Monica Hartnell |
| Tish Hicks |
| Phoebe Holston |
| Michael Hungerford |
| Janis Jones |
| Roy Lee Jones |
| Anna Katarina |
| Barry LeBrock (Un reporter) |
| Emily Lineham |
| Marty Lodge |
| Danielle McKee (Un prisonnier) |
| E.P. McKnight |
| Jim McNichols (Bill Hamlet) |
| Cazimir Milostan |
| Betty Murphy |
| Dave Nemeth |
| Derris Nile |
| James Joseph O'Neil |
| Jeff Daniel Phillips) |
| Carmen Plumb (Janie) |
| David Alan Poe |
| Peter Quartaroli |
| Brett Rickaby (Le détective Roy) |
| Michael Rose |
| Jack Samson (David Graysmith jeune) |
| John Sarno (Donald Harden) |
| Micah Sauers (David Graysmith) |
| Zachary Sauers (Aaron Graysmith) |
| Bill Seward |
| Matthew Shields |
| Ione Skye (Kathleen Johns) |
| Callie Thompson (L'enfant témoin) |
| Cooper Thornton |
| April Vancelette (Un témoin) |
| Cassius M. Willis |
| Shane Woodson |