| Dominic Purcell | Lincoln 'Linc' Burrows |
| Wentworth Miller | Michael Scofield |
| Amaury Nolasco | Fernando Sucre |
| Wade Williams | Brad Bellick |
| Paul Adelstein | Paul Kellerman |
| Robert Knepper | Theodore 'T-Bag' Bagwell |
| Sarah Wayne Callies | Sara Tancredi |
| Rockmond Dunbar | Benjamin Miles 'C-Note' Franklin |
| William Fichtner | Alexander 'Alex' Mahone |
| K.K. Dodds | Susan Hollander |
| Reggie Lee | Bill Kim |
| Sylva Kelegian | Denise |
| Tim DeZarn | Salty Vet |
| Leon Russom | General Jonathan Krantz |
| Jason Davis | FBI Agent Wheeler |
| Phillip Edward Van Lear | Louis Patterson |
| Daniel Allar | Avocado |
| Brandon Smith | Warden Ed Pavelka |
| Dylan Minnette | Young Michael |
| Max Kirsch | Young Lincoln |
| Werner Richmond | Transport Driver |
| Kelly O'Neil Jackson | Transport Guard |
| Justin Meeks | Pilot |
| Louis Gusemano | Border Patrol Officer |
| Ron Gonzalez | Facility Guard |
| Dell Johnson | IDOC Captain |
| Angie Bolling | Judge |
| Eddie Malley | Mahone's Driver |
| Bruce DuBose | Greg Nagel |
| Jason Konopisos-Alvarez | Agent Kim's Aide |
| Andrew Sensenig | Prosecutor |
| Saul Garza | Reporter #2 |
| Heather Hays | Anchor |
| Robert F. Cawley | Cafe Patron |
| Riley Chambers | Fox River Corrections Officer |
| Craig Cole | FBI Agent Eric Houle |
| YaKima Davis | News Reporter |
| Brian Scott Fitzgerald | Border Patrol |
| John Johns | Techie |
| Silas Weir Mitchell | Charles 'Haywire' Patoshik |
| Todd Peters | (uncredited) |
| Daniel Sanchez | FBI Agent |