| 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 |
| Sasha Alexander | Helene Runyon |
| Ever Carradine | Erika |
| Isidora Goreshter | Svetlana |
| Michael McMillian | Tyler |
| Jeff Pierre | Caleb |
| Will Sasso | Yanis |
| Brent Sexton | Patrick Gallagher |
| Andrew Asper | Jason |
| Jaylen Barron | Dominique |
| Melinda Cohen | Georgia |
| Amin El Gamal | Professor Adrian Mitchen |
| Michael Patrick Ferman | Auctioneer
(as Michael Ferman) |
| Jim Hoffmaster | Kermit |
| Rich Hutchman | Peter MacGowan |
| Olga Aguilar | Sarah |
| Owen Alabado | Alex |
| Reuven Bar-Yotam | Pawnbroker |
| Roger V. Burton | Eugene Hamilton |
| Nicole J. Butler | Lysa |
| Sergio Cardenas | Immer |
| Matthew Foster | Porter |
| Thomas Kasp | Barry |
| Daniel W. Kennedy | Tomasz |
| Kellen Michael | Chuckie |
| Victor Onuigbo | Nick
(as Victor I. Onuigbo) |
| Amy Tolsky | Doctor Gillian Barnes |
| Mike Cochrane | Alibi Bar Regular #2
(uncredited) |
| Daniel Gauthier | Cancer Patient
(uncredited) |
| Rafaela Ochoa | High School Soccer Player
(uncredited) |
| Kareem Stroud | Pimp
(uncredited) |
| Livia Treviño | Office Manager
(uncredited) |