| 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 |
| Leo Fitzpatrick | Johnny Weeks |
| J.D. Williams | Preston 'Bodie' Broadus |
| Hassan Johnson | Roland 'Wee-Bey' Brice |
| Michael B. Jordan | Wallace |
| Clayton LeBouef | Wendell 'Orlando' Blocker |
| Melanie Nicholls-King | Cheryl |
| Doug Olear | FBI Spec. Agent Terrance 'Fitz' Fitzhugh |
| Delaney Williams | Sgt. Jay Landsman |
| Richard DeAngelis | Maj. Raymond Foerster |
| Wendy Grantham | Shardene Innes |
| Michael Kostroff | Maurice 'Maury' Levy |
| Michael Salconi | Det. Michael 'Sanny' Santangelo |
| Ingrid Cornell | Nakeesha Lyles |
| Larry Hull | William Gant |
| Lucy Newman-Williams | Asst. State's Atty. Taryn Hanson |
| Michael Stone Forrest | Det. Frank Barlow |
| Nikki Bell | Crack Addict |
| Stephen Szibler | Narcotics Detective |
| Kamal Bostic-Smith | Snot Boogie's Friend |
| Bobby J. Brown | Off. Bobby Brown |
| Tray Chaney | Malik 'Poot' Carr |
| Enrique Chicas | Bailiff |
| Chris Clanton | Savino Bratton |
| Robert F. Colesberry | Det. Ray Cole |
| Aaron Moss | Drug Dealer |
| Brandon Price | Anton 'Stinkum' Artis |
| Ron A. Williams | Addict |