| Dominic West | Det. James 'Jimmy' McNulty |
| John Doman | Maj. William A. Rawls
(credit only) |
| Idris Elba | Russell 'Stringer' Bell |
| Frankie Faison | Dep. Comm. for Operations Ervin H. Burrell
(as Frankie R. Faison) |
| Lawrence Gilliard Jr. | D'Angelo Barksdale
(as Larry Gilliard Jr.) |
| Wood Harris | Avon Barksdale |
| Deirdre Lovejoy | Asst. State's Atty. Rhonda Pearlman |
| Wendell Pierce | Det. William 'Bunk' Moreland |
| Lance Reddick | Lt. Cedric Daniels |
| Andre Royo | Reginald 'Bubbles' Cousins
(credit only) |
| Sonja Sohn | Det. Shakima 'Kima' Greggs
(credit only) |
| Seth Gilliam | Det. Ellis Carver
(credit only) |
| Domenick Lombardozzi | Det. Thomas 'Herc' Hauk |
| Clarke Peters | Det. Lester Freamon |
| Jim True-Frost | Det. Roland 'Prez' Pryzbylewski |
| Michael B. Jordan | Wallace |
| Corey Parker Robinson | Det. Leander Sydnor
(as Corey Parker-Robinson) |
| Wendy Grantham | Shardene Innes |
| J.D. Williams | Preston 'Bodie' Broadus
(as JD Williams) |
| Tray Chaney | Malik 'Poot' Carr |
| Michael Hyatt | Brianna Barksdale |
| Michael Kostroff | Maurice 'Maury' Levy |
| LaTonya Borsay | Orlando's dancer
(as Latonya Borsay) |
| Tony D. Head | Maj. Bobby Reed |
| Michael Salconi | Det. Michael 'Sanny' Santangelo |
| Isiah Whitlock Jr. | State Sen. R. Clayton 'Clay' Davis
(as Isiah Whitlock) |
| Ingrid Cornell | Nakeesha Lyles |
| Jarvis W. George | 'Ronnie Mo' Watkins
(as Jarvis George) |
| Doug Roberts | State's Attorney Steven Demper |
| Giselle Watts | Darcia Wallace |
| Aaron Lee Wright | Fighting Kid |
| Derren Fuentes | Lt. Torret
(uncredited) |
| Joe Gerety | State Trooper
(uncredited) |
| Justin Hinnant | Neighborhood Kid
(uncredited) |
| Mikel Miller | Police Officer
(uncredited) |
| Marcis Turner | Police Officer
(uncredited) |