| William H. Macy | Frank Gallagher |
| Emmy Rossum | Fiona Gallagher |
| Jeremy Allen White | Lip Gallagher |
| Ethan Cutkosky | Carl Gallagher |
| Shanola Hampton | Veronica Fisher |
| Steve Howey | Kevin Ball |
| Emma Kenney | Debbie Gallagher |
| Cameron Monaghan | Ian Gallagher |
| Dermot Mulroney | Sean Pierce |
| Sherilyn Fenn | Queenie |
| Brett Davern | Larry |
| Rick Fox | Gareth |
| Jeff Pierre | Caleb |
| Derek Ray | Gregory |
| Alan Rosenberg | Professor Youens |
| Marcus Folaji Ajose | Lamar
(as Marcus Ajose) |
| Reed Emmons | Will |
| Na'im Lynn | Gangbanger |
| Angeline Appel | Brina |
| Maria Breese | Lina |
| Lawrence Wayne Curry | Vince |
| Calvin Evans | Jerome |
| Barry Finkel | Waiter |
| Marcus Folmar | Erik |
| Bruno Fracassa | Smoking Local |
| Mcabe Gregg | Lain |
| Jee Young Han | Scarlet |
| Sean T. Krishnan | Mr. Jones |
| Stevie Mack | Reynolds |
| Kellen Michael | Chuckie |
| Rachel Rosenstein | Cathy |
| Kyausha Simpson | Rosette |
| Stephen Rider | G-Dogg |
| Jocelin Albor | Girl with Lip
(uncredited) |
| Sasha Alexander | Helene Runyon
(uncredited) |
| Cesar Azanza | Move Theatre Patron
(uncredited) |
| Mike Cochrane | Alibi Bar Regular #2
(uncredited) |
| Brenden Sims | Liam Gallagher
(uncredited) |