| Dominic West | Det. James 'Jimmy' McNulty |
| Reg E. Cathey | Norman Wilson |
| John Doman | Dep. Comm. for Operations William A. Rawls |
| Aidan Gillen | Mayor Thomas 'Tommy' Carcetti |
| Clark Johnson | City Editor Augustus 'Gus' Haynes |
| Deirdre Lovejoy | Asst. State's Atty. Rhonda Pearlman |
| Tom McCarthy | Scott Templeton |
| Clarke Peters | Det. Lester Freamon |
| Wendell Pierce | Det. William 'Bunk' Moreland |
| Lance Reddick | Col. Cedric Daniels
(credit only) |
| Andre Royo | Reginald 'Bubbles' Cousins |
| Sonja Sohn | Det. Shakima 'Kima' Greggs |
| Seth Gilliam | Sgt. Ellis Carver
(credit only) |
| Domenick Lombardozzi | Thomas 'Herc' Hauk
(credit only) |
| Michael Kenneth Williams | Omar Little
(credit only) |
| Gbenga Akinnagbe | Chris Partlow |
| Jamie Hector | Marlo Stanfield |
| Neal Huff | Chief of Staff Michael Steintorf |
| Jermaine Crawford | Duquan 'Dukie' Weems |
| Corey Parker Robinson | Det. Leander Sydnor |
| Tristan Mack Wilds | Michael Lee
(as Tristan Wilds) |
| Michael Kostroff | Maurice 'Maury' Levy
(credit only) |
| Michelle Paress | Alma Gutierrez |
| Isiah Whitlock Jr. | State Sen. R. Clayton 'Clay' Davis |
| Frankie Faison | Commissioner Ervin H. Burrell |
| Wood Harris | Avon Barksdale |
| Steve Earle | Walon |
| Felicia Pearson | Felicia 'Snoop' Pearson |
| Delaney Williams | Sgt. Jay Landsman |
| Chris Ashworth | Sergei 'Serge' Malatov |
| Genevieve Hudson-Price | Dee Dee |
| Frederick Strother | State Delegate Odell Watkins |
| Benay Berger | FBI Supervisor Amanda Reese |
| Doug Olear | FBI Spec. Agent Terrance 'Fitz' Fitzhugh |
| Joe Urla | U.S. Attorney for the District of Maryland
(as Joseph Urla) |
| David Costabile | Managing Editor Thomas Klebanow |
| Sam Freed | Executive Editor James C. Whiting III |
| Donald Neal | Rewrite Man Jay Spry |
| Bobby J. Brown | Off. Bobby Brown
(as Bobby Brown) |
| Anthony Mangano | Det. Kevin Infante |
| Kristie Dale Sanders | Det. Nancy Porter |
| Gregory L. Williams | Det. Michael Crutchfield |
| Bruce Kirkpatrick | Roger Twigg |
| Thomas J. McCarthy | State Editor Tim Phelps
(as Tom McCarthy) |
| Kara Lee Duncan | Regional Affairs Editor Rebecca Corbett
(as Kara Quick) |
| Todd Scofield | Jeff Price |
| Darrell Britt-Gibson | Darius 'O-Dog' Hill |
| Kwame Patterson | 'Monk' Metcalf |
| Scott Shane | Scott Shane |
| Suzanne Wooton | Suzanne Wooton |
| Willa Bickham | Willa Bickham |
| Dan Manning | Asst. Medical Examiner |
| Kate Revelle | Jane |
| Kelley Slagle | Asst. Medical Examiner |
| Brendan Walsh | Brendan Walsh |
| Erica Chamblee | Pregnant Woman |
| Lee E. Cox | Off. Aaron Castor
(as Lee Everett Cox) |
| Rachel Lynn Dinenna | Woman |
| Frank McPartland | Angry Baseball Fan |
| Andrew Roth | Tim Packard |
| Tasha Rudolph | Abusive Mother
(as Tasha R. Rudolph) |
| Andrew Cruttenden | Man |
| Ayoka Dorsey | Gus's Wife |
| Tyson Hall | Marvin |
| Adrienne Meisel | Recovering addict |
| Patricia Penn | Sun Staff Member |
| Steve Zettler | Prison Guard |
| Louis Stancil | Unknown Corner Boy
(archive footage) |
| Tex Allen | Newspaper Copy Editor
(uncredited) |
| Nora Bauer | Waitress
(uncredited) |
| Anthony Bosco | The Sun Copy Editor
(uncredited) |
| Curt Boushel | Andy
(uncredited) |
| Dave Ehrman | Researcher
(uncredited) |
| Art Hall | Reporter
(uncredited) |
| Elizabeth Mary Nolan | Reporter
(uncredited) |
| Jennifer Rouse | Whiting's Secretary
(uncredited) |
| Kevyn Settle | Sun Paper Layout Editor
(uncredited) |
| Michael James Shaw | Homeless Man
(uncredited) |
| Patrick Michael Strange | Reporter
(uncredited) |
| Lace Williams | Homeless Girl
(uncredited) |