| 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
(credit only) |
| Wendell Pierce | Det. William 'Bunk' Moreland |
| 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
(as JD Williams) |
| Michael Kenneth Williams | Omar Little
(as Michael K. Williams) |
| Corey Parker Robinson | Det. Leander Sydnor
(credit only) |
| Glynn Turman | Mayor Clarence V. Royce |
| Isiah Whitlock Jr. | State Sen. R. Clayton 'Clay' Davis |
| Chad L. Coleman | Dennis 'Cutty' Wise |
| Jamie Hector | Marlo Stanfield |
| Maria Broom | Marla Daniels |
| Michael Hyatt | Brianna Barksdale |
| Delaney Williams | Sgt. Jay Landsman |
| Brandy Burre | Theresa D'Agostino |
| Benjamin Busch | Off. Anthony Colicchio |
| Jay Landsman | Lt. Dennis Mello |
| Megan Anderson | Jen Carcetti |
| Shamyl Brown | Donette |
| Verna Day | Resident
(as Verna Lee Day) |
| Anwan Glover | Slim Charles |
| Kelli R. Brown | Kimmy |
| Richard DeAngelis | Col. Raymond Foerster |
| Nina Hodoruk | State's Atty. Kendall Remnick |
| Michael Salconi | Off. Michael 'Sanny' Santangelo |
| Ernest Waddell | Dante |
| Mayo Best | Gerard |
| Richard Burton | Sean 'Shamrock' McGinty |
| Norris Davis | Vinson |
| Brandon Fobbs | Fruit |
| Addison Switzer | Country |
| Gbenga Akinnagbe | Chris Partlow |
| Christopher Mann | Councilman Anthony 'Tony' Gray |
| Cleo Reginald Pizana | Chief of Staff Coleman Parker |
| Frederick Strother | State Delegate Odell Watkins |
| Michael Willis | Andy Krawczyk |
| Demetria Bailey | Tonia's Sister
(uncredited) |
| R. Emery Bright | Community Relations Sgt.
(uncredited) |
| Vicki Jean Clark | Parent
(uncredited) |
| Brian Edwards | Undercover Police Officer
(uncredited) |
| Edward Bernard Green Jr. | Spider
(uncredited) |
| Rae Haskins | Drug Dealer
(uncredited) |
| Dana Jay | Gangmember (Omars Crew) Camera Man
(uncredited) |
| Walter Wiz Nichols | Street Guy
(uncredited) |
| Felicia Pearson | Felicia 'Snoop' Pearson
(uncredited) |
| Vito Pietanza | FBI Agent
(uncredited) |
| Ryan Sands | Off. Lloyd 'Truck' Garrick
(uncredited) |
| Thomas W. Stewart | Parent
(uncredited) |
| Esley Tate | Boo
(uncredited) |
| Shaun Woodland | Dealer #2
(uncredited) |