| Dominic West | Det. James 'Jimmy' McNulty |
| John Doman | Maj. William A. Rawls |
| Idris Elba | Russell 'Stringer' Bell |
| Frankie Faison | Dep. Comm. for Operations Ervin H. Burrell |
| Lawrence Gilliard Jr. | D'Angelo Barksdale |
| 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 |
| Sonja Sohn | Det. Shakima 'Kima' Greggs |
| Peter Gerety | Judge Daniel Phelan |
| Seth Gilliam | Det. Ellis Carver |
| Domenick Lombardozzi | Det. Thomas 'Herc' Hauk |
| Clarke Peters | Det. Lester Freamon |
| Jim True-Frost | Det. Roland 'Prez' Pryzbylewski |
| Maria Broom | Marla Daniels |
| J.D. Williams | Preston 'Bodie' Broadus |
| Hassan Johnson | Roland 'Wee-Bey' Brice |
| Michael B. Jordan | Wallace |
| Corey Parker Robinson | Det. Leander Sydnor |
| Tom Quinn | Det. Patrick Mahon |
| Michael Salconi | Det. Michael 'Sanny' Santangelo |
| Delaney Williams | Sgt. Jay Landsman |
| Richard DeAngelis | Maj. Raymond Foerster |
| Nat Benchley | Det. Augustus Polk |
| Shamyl Brown | Donette |
| Tray Chaney | Malik 'Poot' Carr |
| Erik Dellums | Dr. Randall Frazier |
| Michael Kostroff | Maurice 'Maury' Levy |
| Brandon Price | Anton 'Stinkum' Artis |
| Dave Trovato | Lt. Walter Cantrell |
| Walter Simpson III | Crack Cocaine Addict |
| Dakota Anderson | Sniper |
| Chris Clanton | Savino Bratton |
| Robert F. Colesberry | Det. Ray Cole |
| Jarvis W. George | 'Ronnie Mo' Watkins |
| Rodney J. Hobbs | Police Officer |
| Micaiah Jones | Wintell 'Little Man' Royce |
| Jimmie Jelani Manners | Kevin Johnston |
| Aaron Moss | Drug Dealer |
| Aaron J. Savage | Barksdale Crew Member |