| Dominic West | Off. James 'Jimmy' McNulty |
| John Doman | Dep. Comm. for Operations William A. Rawls |
| Frankie Faison | Commissioner Ervin H. Burrell |
| Aidan Gillen | Mayor Thomas 'Tommy' Carcetti |
| Deirdre Lovejoy | Asst. State's Atty. Rhonda Pearlman |
| Clarke Peters | Det. Lester Freamon |
| Wendell Pierce | Det. William 'Bunk' Moreland |
| Lance Reddick | Col. Cedric Daniels |
| Andre Royo | Reginald 'Bubbles' Cousins |
| Sonja Sohn | Det. Shakima 'Kima' Greggs |
| Jim True-Frost | Roland 'Prez' Pryzbylewski |
| Robert Wisdom | Howard 'Bunny' Colvin |
| Seth Gilliam | Sgt. Ellis Carver |
| Domenick Lombardozzi | Sgt. Thomas 'Herc' Hauk |
| Reg E. Cathey | Norman Wilson |
| Chad L. Coleman | Dennis 'Cutty' Wise |
| Jamie Hector | Marlo Stanfield |
| Glynn Turman | Former Mayor Clarence V. Royce
(credit only) |
| J.D. Williams | Preston 'Bodie' Broadus
(as JD Williams) |
| Michael Kenneth Williams | Omar Little
(as Michael K. Williams) |
| Corey Parker Robinson | Det. Leander Sydnor |
| Paul Ben-Victor | Spiros 'Vondas' Vondopoulos |
| Amy Ryan | Off. Beatrice 'Beadie' Russell |
| Isiah Whitlock Jr. | State Sen. R. Clayton 'Clay' Davis |
| Jermaine Crawford | Duquan 'Dukie' Weems |
| Maestro Harrell | Randy Wagstaff |
| Julito McCullum | Namond Brice |
| Tristan Mack Wilds | Michael Lee
(as Tristan Wilds) |
| Gbenga Akinnagbe | Chris Partlow |
| Hassan Johnson | Roland 'Wee-Bey' Brice |
| Jay Landsman | Lt. Dennis Mello |
| Edward T. Norris | Det. Edward Norris
(as Ed Norris) |
| Delaney Williams | Sgt. Jay Landsman |
| Robert F. Chew | Joseph 'Proposition Joe' Stewart |
| Steve Earle | Walon |
| Anwan Glover | Slim Charles |
| Method Man | Melvin 'Cheese' Wagstaff |
| Kelli R. Brown | Kimmy |
| Tray Chaney | Malik 'Poot' Carr |
| S. Robert Morgan | Butchie |
| Ramon Rodriguez | Renaldo |
| Stacie Davis | Ms. Duquette |
| Dan De Luca | David Parenti
(as Dan DeLuca) |
| Neal Huff | Chief of Staff Michael Steintorf |
| Dravon James | Grace Sampson |
| Cleo Reginald Pizana | Coleman Parker |
| Taylor King | Zenobia Dawson |
| Jeffrey Lorenzo | Karim Williams |
| Rakiya Orange | Charlene Young |
| Felicia Pearson | Felicia 'Snoop' Pearson |
| Rico Sterling | Calvin |
| Jason Wharton | Albert Stokes |
| Keenon Brice | Aaron 'Bug' Manigault |
| Nathan Corbett | Donut |
| Thuliso Dingwall | Kenard |
| Shenia Hatchett | Woman |
| Destiny Jackson-Evans | Crystal Judkins |
| Na'Dria Jennings | Chandra Porter |
| Gary D'Addario | Grand Jury Prosecutor Gary DiPasquale |
| Darrell Britt-Gibson | Darius 'O-Dog' Hill |
| Edward Bernard Green Jr. | Spider
(as Edward Green) |
| Sandi McCree | De'Londa Brice |
| Kwame Patterson | 'Monk' Metcalf |
| Troj Strickland | Ricardo 'Fat Face Rick' Hendrix
(as Troj. Marquis Strickland) |
| Megan Anderson | Jen Carcetti |
| Sheila Gaskins | Mrs. Anderson |
| Reginald Gilmer | Man |
| Duane Chandler Rawlings | Nathaniel 'Hungry Man' Manns |
| Michael Salconi | Off. Michael 'Sanny' Santangelo |
| Karen Vicks | Gerry |
| Gregory L. Williams | Det. Michael Crutchfield |
| Michael Ahl | Detective
(uncredited) |
| Mike D. Anderson | Ghost
(uncredited) |
| Larry Andrews | Donnie
(uncredited) |
| Sho Brown | Phil Boy
(uncredited) |
| Benjamin Busch | Off. Anthony Colicchio
(uncredited) |
| Allyn Camp | Detention Officer
(uncredited) |
| David DeBoy | Detective Shea
(uncredited) |
| Skye Dennis | Paramedic
(uncredited) |
| Brian Dragonuk | Reporter
(uncredited) |
| Robert Guillaume | Benson DuBois
(archive footage) (uncredited) |
| Bethany Hoffman | Paramedic
(uncredited) |
| Marcus LaRon | Police Officer
(uncredited) |
| David L. Marston | Newspaper Photographer
(uncredited) |
| Ian McShane | Al Swearengen
(archive footage) (uncredited) |
| Rick Otto | Off. Kenneth Dozerman
(uncredited) |
| Norman Outlaw | Orderly
(uncredited) |
| Ryan Sands | Off. Lloyd 'Truck' Garrick
(uncredited) |
| Marvina Vinique | Nurse
(uncredited) |
| Stephen Zaleski | Coroner
(uncredited) |