| Dominic West | Jimmy McNulty |
| Lance Reddick | Cedric Daniels |
| Sonja Sohn | Kima Greggs |
| Wood Harris | Avon Barksdale |
| Wendell Pierce | Bunk Moreland |
| Clarke Peters | Lester Freamon |
| Michael Kenneth Williams | Omar Little |
| Deirdre Lovejoy | Rhonda Pearlman |
| J.D. Williams | Bodie Broadus |
| Andre Royo | Bubbles |
| Seth Gilliam | Ellis Carver |
| Frankie Faison | Ervin Burrell |
| Domenick Lombardozzi | Herc |
| Corey Parker Robinson | Leander Sydnor |
| Isiah Whitlock Jr. | Clay Davis |
| Michael Kostroff | Maurice Levy |
| John Doman | William Rawls |
| Hassan Johnson | Roland 'Wee-Bay' Brice |
| Tray Chaney | Malik 'Poot' Carr |
| John Doman | William Rawls |
| Delaney Williams | Sgt. Jay Landsman |
| Pablo Schreiber | Nick Sobotka |
| Chris Ashworth | Sergei 'Serge' Malatov |
| Charley Scalies | Thomas 'Horseface' Pakusa |
| Melanie Nicholls-King | Cheryl |
| Chris Bauer | Frank Sobotka |
| Paul Ben-Victor | Spiros 'Vondas' Vondopoulos |
| James Ransone | Chester 'Ziggy' Sobotka |
| Al Brown | Maj. Stanislaus Valchek |
| Bill Raymond | The Greek |
| Jim True-Frost | Det. Roland 'Prez' Pryzbylewski |
| Robert F. Colesberry | Det. Ray Cole (uncredited) |