| Dominic West | Off. James 'Jimmy' McNulty |
| Chris Bauer | Frank Sobotka |
| Paul Ben-Victor | Spiros 'Vondas' Vondopoulos |
| John Doman | Col. William A. Rawls |
| Idris Elba | Russell 'Stringer' Bell |
| Frankie Faison | Acting Commissioner Ervin H. Burrell |
| Wood Harris | Avon Barksdale |
| Deirdre Lovejoy | Asst. State's Atty. Rhonda Pearlman |
| Clarke Peters | Det. Lester Freamon |
| Wendell Pierce | Det. William 'Bunk' Moreland |
| Lance Reddick | Lt. Cedric Daniels |
| Amy Ryan | Off. Beatrice 'Beadie' Russell |
| Sonja Sohn | Det. Shakima 'Kima' Greggs |
| Seth Gilliam | Sgt. Ellis Carver |
| Domenick Lombardozzi | Det. Thomas 'Herc' Hauk |
| Jim True-Frost | Det. Roland 'Prez' Pryzbylewski |
| Robert Wisdom | Maj. Howard 'Bunny' Colvin |
| James Ransone | Chester 'Ziggy' Sobotka |
| Pablo Schreiber | Nick Sobotka |
| Tom Mardirosian | Agent Kristos Koutris |
| Michael Potts | Brother Mouzone |
| Bill Raymond | The Greek |
| Lev Gorn | Eton Ben-Eleazer |
| Michael Hyatt | Brianna Barksdale |
| J.D. Williams | Preston 'Bodie' Broadus |
| Tray Chaney | Malik 'Poot' Carr |
| Robert F. Chew | Joseph 'Proposition Joe' Stewart |
| Luray Cooper | Nathaniel 'Nat' Coxson |
| Kelvin Davis | La La |
| Chris Ashworth | Sergei 'Serge' Malatov |
| Al Brown | Maj. Stanislaus Valchek |
| Doug Olear | FBI Spec. Agent Terrance 'Fitz' Fitzhugh |
| Charley Scalies | Thomas 'Horseface' Pakusa |
| Delaney Williams | Sgt. Jay Landsman |
| Teddy Cañez | George 'Double G' Glekas |
| Bus Howard | Vernon 'Ott' Motley |
| Edward T. Norris | Det. Edward Norris |
| Gloria Phillips | Bereaved Mother |
| David Barroso | Swat Team Mike Serano |
| Randall Boffman | Bill Anderson - Port Admin. Port of Baltimore |
| Richard Burton | Sean 'Shamrock' McGinty |
| Elizabeth J. Carlisle | Prostitute |
| Robert F. Colesberry | Det. Ray Cole |
| Gil Deeble | Hucklebuck |
| Derren Fuentes | Lt. Torret |
| Jeffrey Pratt Gordon | John 'Johnny Fifty' Spamanto |
| Jonas Grey | Drug Buyer |
| De'Rodd Hearns | Herbert De'Rodd 'Puddin' Johnson |
| Jay Landsman | Lt. Dennis Mello |
| Gordana Rashovich | Ilona Petrovich |
| Jill Redding | Delores |
| Brook Yeaton | Michael 'White Mike' McArdle |