| Dominic West | Det. James 'Jimmy' McNulty |
| John Doman | Dep. Comm. for Operations William A. Rawls |
| Idris Elba | Russell 'Stringer' Bell |
| Frankie Faison | Acting Commissioner Ervin H. Burrell
(credit only) |
| Aidan Gillen | Councilman Thomas 'Tommy' Carcetti |
| Wood Harris | Avon Barksdale |
| Deirdre Lovejoy | Asst. State's Atty. Rhonda Pearlman |
| Clarke Peters | Det. Lester Freamon |
| Wendell Pierce | Det. William 'Bunk' Moreland
(credit only) |
| Lance Reddick | Lt. Cedric Daniels |
| Andre Royo | Reginald 'Bubbles' Cousins |
| Sonja Sohn | Det. Shakima 'Kima' Greggs |
| Jim True-Frost | Det. Roland 'Prez' Pryzbylewski |
| Robert Wisdom | Maj. Howard 'Bunny' Colvin |
| Seth Gilliam | Sgt. Ellis Carver |
| Domenick Lombardozzi | Det. Thomas 'Herc' Hauk |
| J.D. Williams | Preston 'Bodie' Broadus
(as JD Williams) |
| Michael Kenneth Williams | Omar Little
(as Michael K. Williams) |
| Corey Parker Robinson | Det. Leander Sydnor |
| Isiah Whitlock Jr. | State Sen. R. Clayton 'Clay' Davis |
| Chad L. Coleman | Dennis 'Cutty' Wise |
| Michael Hyatt | Brianna Barksdale |
| Maria Broom | Marla Daniels |
| Brandy Burre | Theresa D'Agostino |
| Delaney Williams | Sgt. Jay Landsman |
| Robert F. Chew | Joseph 'Proposition Joe' Stewart |
| Doug Olear | FBI Spec. Agent Terrance 'Fitz' Fitzhugh |
| Melvin Williams | Deacon |
| Christopher Mann | Councilman Anthony 'Tony' Gray |
| Ryan Sands | Off. Lloyd 'Truck' Garrick |
| Brandan T. Tate | Sapper |
| Brian Anthony Wilson | Det. Vernon Holley |
| Mayo Best | Gerard |
| Kim Bogues | Woman |
| Richard Burton | Sean 'Shamrock' McGinty |
| Anwan Glover | Slim Charles |
| Kelli R. Brown | Kimmy |
| Mia Arnice Chambers | Squeak |
| Melvin Jackson Jr. | Bernard |
| Felix Stevenson | Rev. Frank Reid |
| Ernest Waddell | Dante |
| Al Brown | Maj. Stanislaus Valchek |
| Norris Davis | Vinson |
| Richard DeAngelis | Col. Raymond Foerster |
| Frederick Strother | State Delegate Odell Watkins |
| Gregory L. Williams | Det. Michael Crutchfield |
| Benay Berger | FBI Supervisor Amanda Reese |
| Antonio Cordova | Michael McNulty
(as Tony Cordova) |
| Eric G. Ryan | Sean McNulty
(as Eric Ryan) |
| Michael Salconi | Off. Michael 'Sanny' Santangelo |
| Troj Strickland | Ricardo 'Fat Face Rick' Hendrix
(as Troj. Marquis Strickland) |
| Mike D. Anderson | Ghost
(uncredited) |
| James E. Ash | Uniform Officer
(uncredited) |
| Akim Black | Off. Tope
(uncredited) |
| Sho Brown | Phil Boy
(uncredited) |
| Benjamin Busch | Off. Anthony Colicchio
(uncredited) |
| Kimberly S. Fairbanks | Patrolwoman
(uncredited) |
| Keith Johnson | Desk Sergeant
(uncredited) |
| Jim Klock | Off. Gillan
(uncredited) |
| Marcus LaRon | Police Officer
(uncredited) |
| Tommy Lee Taylor Jr. | Lester Sanders
(uncredited) |
| Shaun Woodland | Dealer #2
(uncredited) |