| 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 |
| Delaney Williams | Sgt. Jay Landsman |
| Method Man | Melvin 'Cheese' Wagstaff |
| Rick Otto | Off. Kenneth Dozerman |
| Gbenga Akinnagbe | Chris Partlow (uncredited) |
| Felicia Pearson | Felicia 'Snoop' Pearson |
| Isiah Whitlock Jr. | State Sen. R. Clayton 'Clay' Davis (uncredited) |
| Maestro Harrell | Randy Wagstaff |
| Mike D. Anderson | Ghost (uncredited) |
| Chad L. Coleman | Dennis 'Cutty' Wise |
| Ramón Rodríguez | Renaldo |
| Amy Ryan | Off. Beatrice 'Beadie' Russell |