| Steve Buscemi | Enoch 'Nucky' Thompson |
| Kelly Macdonald | Margaret Thompson |
| Michael Shannon | Nelson Van Alden |
| Shea Whigham | Elias 'Eli' Thompson |
| Michael Stuhlbarg | Arnold Rothstein |
| Stephen Graham | Al Capone |
| Vincent Piazza | Lucky Luciano |
| Michael Kenneth Williams | Chalky White |
| Anthony Laciura | Eddie Kessler |
| Paul Sparks | Mickey Doyle |
| Jack Huston | Richard Harrow |
| Charlie Cox | Owen Sleater |
| Bobby Cannavale | Gyp Rosetti |
| Gretchen Mol | Gillian Darmody |
| Anatol Yusef | Meyer Lansky |
| Nick Robinson | Rowland Smith - Nate's Partner |
| Patrick Kennedy | Dr. Douglas Mason |
| Kerry O'Malley | Mrs. Edwina Shearer |
| Ivo Nandi | Joe Masseria |
| Heather Lind | Katy |
| Lucas Caleb Rooney | Joe Miller - O'Banion's Man |
| Joseph Aniska | Agent Stan Sawicki |
| Brendan Burke | Mickey's Driver |
| Chris Caldovino | Tonino Sandrelli |
| Joe Caniano | Jake Guzik |
| James Ciccone | Joe Masseria's Thug |
| Frank Deal | Mr. Franklin Shearer |
| Marc D. Donovan | Deputy Ramsey |
| Alex Eckstein | Sonny Capone |
| Ben Eckstein | Sonny Capone |
| Caleb Eckstein | Sonny Capone |
| Michael Louis Gibson | Owen's Man |
| Chris Haag | Philadelphia Prohibition Agent 1 |
| Ed Heavey | Tunney |
| James Hosey | Mickey's Delivery Boy |
| David Edward Jackson | Gas Jockey |
| Marcella Lentz-Pope | Mae Capone |
| Paul Locke | Rosetti Thug |
| Rebecca Luker | Sister Agnes |
| Margo Seibert | Uppity Nanny |
| Michael Solomon | Philadelphia Prohibition Agent 2 |
| Katy Wright-Mead | Roberta |
| Michael Zegen | Benny Siegel |
| Joseph Dimartino | Four Deuces Bartender |
| Steve Fogelman | Ritz Hotel Doorman |
| David Itchkawitz | Upscale Citizen |
| Billy Joe Kiessling | Driver |
| Finian Montague | Shearer's Son |
| Will Sandoval | WWI Veteran |