| 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 |
| Steve Kazee | Gus Pfender |
| Sasha Alexander | Helene Runyon |
| Nichole Sakura | Amanda
(as Nichole Bloom) |
| Ever Carradine | Erika |
| Isidora Goreshter | Svetlana |
| José Julián | Joaquin
(as Jose Julian) |
| Jeff Pierre | Caleb |
| Alan Rosenberg | Professor Youens |
| Jim Hoffmaster | Kermit |
| Rich Hutchman | Peter MacGowan |
| Michael Patrick McGill | Tommy |
| Rebecca Metz | Melinda |
| Victor Onuigbo | Nick
(as Victor I. Onuigbo) |
| George Wyner | Board Member |
| Owen Alabado | Alex |
| Steve Bean | Abe |
| Roxanne Beckford | Dr. Pau |
| Reed Emmons | Will |
| Casey Kringlen | Suspicious Dude |
| Peyton Elizabeth Lee | Girl Soldier |
| Dinah Lenney | Frannie |
| James Lentzsch | Topknot Dude |
| Jonathan Medina | Dr. Ruiz |
| Kellen Michael | Chuckie |
| Leslie L. Miller | Beat-Up Woman |
| Jaquita Ta'le | Jada |
| Dan Waller | Rod |
| Mike Cochrane | Alibi Bar Regular #2
(uncredited) |
| Asher McDonell | Baby
(uncredited) |
| Brayden McDonell | Baby
(uncredited) |
| Lotus Plummer | Amy /
Jemma Ball
(uncredited) |
| Alex Zelenka | College Student
(uncredited) |