| 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 |
| Isidora Goreshter | Svetlana Fisher
(credit only) |
| Dermot Mulroney | Sean Pierce |
| Juliette Angelo | Geneva |
| Scott Michael Campbell | Brad |
| Dale Dickey | Aunt Ronnie |
| Elliot Fletcher | Trevor |
| Ruby Modine | Sierra |
| Jessica Szohr | Nessa |
| Raffi Barsoumian | Bahir |
| Bre Blair | Cynthia |
| Christian Isaiah | Liam Gallagher |
| Jennifer Taylor | Anne Seery |
| Levy Tran | Eddie |
| Blake Altounian | Dorian |
| Melinda Chilton | Coach Shaw |
| Quincy Cho | Cyndi |
| Carolyn Crotty | Mary |
| Michael Delgado | JJ (Junkie Jones) |
| Anthony L. Fernandez | Maceo |
| Cassie Hernandez | Mimi |
| Jenna Anne Johnson | Bambi |
| Jill Johnson | Tilly
(as Jill Lynne Johnson) |
| Jane Morris | Berta |
| Scott Peat | Biff |
| Benjamin Plessala | Brenan |
| Kim Robillard | Uncle Travis |
| Malkia Stampley | Lula |
| Steve Suh | Rocky |
| London Thor | Olivia |
| Alexanne Wagner | Baddest Chick |
| Ashley Wood | Beverly |
| Dallas Young | De'Andre
(as Dallas Dupree Young) |
| Anthony Bratts | Mary's Husband
(uncredited) |
| Tierra Amira Jones | Biff's Wife
(uncredited) |
| Kris Mardula | Businessman
(uncredited) |