| 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 |
| Steve Kazee | Gus Pfender |
| Sherilyn Fenn | Queenie |
| Isidora Goreshter | Svetlana |
| Emma Greenwell | Mandy Milkovich |
| Pat Healy | Lester |
| Jeff Kober | Jupiter |
| Oscar Nuñez | Rick Encarnacion
(as Oscar Nunez) |
| Jayne Taini | Harmony |
| Angeline Appel | Brina |
| Jaylen Barron | Dominique |
| Julie Claire | Barbara Klifton |
| Reuven Bar-Yotam | Pawnbroker |
| Janna Bossier | Receptionist |
| Yelyna De Leon | Nurse |
| Monica Estrada | Mrs. Gonzales |
| Matt Gottlieb | Tahuti |
| Stacie Greenwell | Olga |
| David Gurrola | Ernesto |
| Kellen Michael | Chuckie |
| Camden Toy | Pan |
| Cici Leah Campbell | Hippie Cult Member
(uncredited) |
| Mike Cochrane | Alibi Bar Regular #2
(uncredited) |
| Derek Hahn | Chicago Polytechnic Student
(uncredited) |
| Asher McDonell | Baby
(uncredited) |
| Brayden McDonell | Baby
(uncredited) |
| Brenden Sims | Liam Gallagher
(uncredited) |
| Hans Dieter Wolff | Frank's Neighbor
(uncredited) |