| 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 |
| Richard Flood | Ford Kellogg |
| Christian Isaiah | Liam Gallagher |
| Scott Michael Campbell | Brad |
| Samantha Hanratty | Kassidi
(as Sammi Hanratty) |
| Amirah Johnson | Xan |
| Lex Medlin | Dr. Jonathan Rosenbaum |
| Kate Miner | Tami Tamietti |
| Glenn Plummer | Jacob |
| Jim Hoffmaster | Kermit |
| Michael Patrick McGill | Tommy |
| Peter Banifaz | Farhad |
| Andrew Bowen | Darren |
| Monika Casey | Sasha |
| Cristen Coppen | Greta |
| Jackson Davis | Ed Bragg |
| Ben D. Goldberg | Edgar |
| Rif Hutton | General Gene Powell |
| Fernando Martinez | Joselito |
| Maximilian Osinski | Len Martini |
| Alison Rood | Irene Bragg |
| Jennifer Taylor | Anne Seery |
| Ashley Wood | Beverly Martini |
| Marcus Ashley | Wells Stewart |
| Rachel Leah Cohen | Molly |
| Glen Davis | Jules |
| Sapna Gandhi | Charlize Stewart |
| Jason Jin | Richard |
| William Leon | Raul Padilla |
| Robert Ochoa | Dave Huntington |
| Melissa Paladino | Cami |
| Laura Patalano | Daysi |
| Dino Petrera | Leo |
| Brett-Livingstone Strong II | Ted |
| Frank Trigg | Guard |
| Chad Bonsack | Joselito's Posse Inmate
(uncredited) |
| Jeni Jones | Brad's Friend
(uncredited) |
| Sarah Langdon | Docent
(uncredited) |
| Cadence Murray | School Girl
(uncredited) |
| Presley Schrader | Franny
(uncredited) |
| Alex Zelenka | Pedestrian
(uncredited) |