| 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 |
| 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
(credit only) |
| Robert Wisdom | Maj. Howard 'Bunny' Colvin |
| Seth Gilliam | Sgt. Ellis Carver |
| Domenick Lombardozzi | Det. Thomas 'Herc' Hauk |
| J.D. Williams | Preston 'Bodie' Broadus
(voice) (as JD Williams) |
| Michael Kenneth Williams | Omar Little
(as Michael K. Williams) |
| Corey Parker Robinson | Det. Leander Sydnor |
| Glynn Turman | Mayor Clarence V. Royce |
| Peter Gerety | Judge Daniel Phelan |
| Chad L. Coleman | Dennis 'Cutty' Wise |
| Jamie Hector | Marlo Stanfield |
| Brandy Burre | Theresa D'Agostino |
| Michael Potts | Brother Mouzone |
| Melvin Williams | Deacon |
| Robert F. Chew | Joseph 'Proposition Joe' Stewart |
| Richard Burton | Sean 'Shamrock' McGinty |
| Anwan Glover | Slim Charles |
| DeAndre McCullough | Lamar
(as De'Andre McCullough) |
| S. Robert Morgan | Butchie |
| Gbenga Akinnagbe | Chris Partlow |
| Megan Anderson | Jen Carcetti |
| R. Emery Bright | Community Relations Sgt. |
| Norris Davis | Vinson |
| Jay Landsman | Lt. Dennis Mello |
| Sho Brown | Phil Boy
(as Sho 'Swordsman' Brown) |
| Tony D. Head | Maj. Bobby Reed |
| Marty Lodge | Banisky |
| Felicia Pearson | Felicia 'Snoop' Pearson |
| Cleo Reginald Pizana | Chief of Staff Coleman Parker |
| Mia Arnice Chambers | Squeak |
| Tiara Harris | Devonne
(as Tianna Harris) |
| Melvin Jackson Jr. | Bernard |
| Troj Strickland | Ricardo 'Fat Face Rick' Hendrix
(as Troj. Marquis Strickland) |
| Brian Anthony Wilson | Det. Vernon Holley |
| Justin Burley | Justin
(uncredited) |
| Bruce Allen Dawson | Bar Patron
(uncredited) |
| Nakia Dillard | Off. Lambert
(uncredited) |
| Kahil Dotay | Undercover Street Cop
(uncredited) |
| Brandon Fobbs | Fruit
(uncredited) |
| Edward Bernard Green Jr. | Spider
(uncredited) |
| Joilet Harris | Off. Caroline Massey
(uncredited) |
| Marc Krinsky | Angelo Martin
(uncredited) |
| Raw Leiba | Stringer's Bodyguard
(uncredited) |
| Karl Otter | District Commander
(uncredited) |
| Vito Pietanza | FBI Agent
(uncredited) |
| Melvin T. Russell | Jamal
(uncredited) |
| Ryan Sands | Off. Lloyd 'Truck' Garrick
(uncredited) |
| Rico Sterling | Tyrell
(uncredited) |
| Ernest Waddell | Dante
(uncredited) |
| Edonis Washington | Latroy
(uncredited) |
| John Wooten | Off. Terry Garner
(uncredited) |
| Lee Zagari | Juan
(uncredited) |
| Stephen Zaleski | Coroner
(uncredited) |