| 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 |
| Dan Lauria | Mo White |
| Scott Michael Campbell | Brad |
| Patrick Davis Alarcón | Jason
(as Patrick Davis) |
| Paul Dooley | Ralph |
| Amirah Johnson | Xan |
| Sari Lennick | Rabbi |
| Ashley Romans | Alex |
| Don Stark | Congressman Wayne Ubberman |
| Jim Hoffmaster | Kermit |
| Michael Patrick McGill | Tommy |
| Bruce Robert Cole | Priest |
| Angel Laketa Moore | Denise |
| Steven M. Porter | Craig |
| Sarah Assumma | Sissy |
| Betsy Baker | Janice |
| Roberta Bassin | Mrs. Winston
(as Roberta E. Bassin) |
| Drea Garcia | Nurse Telma |
| Pramode Kumar | Punna |
| Jin Maley | Makayla
(as Lisa Maley) |
| Griffin Morgan | Tyrell |
| Emily Nelson | Evelyn Thomas |
| Ozie Nzeribe | Todd |
| Irene Roseen | Mrs. Riley |
| Jessica Rosilyn | Dee Sanders |
| Presley Schrader | Franny |
| Mike Cochrane | Alibi Regular
(uncredited) |
| Kaytie Kellaway | Russian Prostitute
(uncredited) |
| Cindy Le | Debbie's Welding Friend
(uncredited) |
| Alex Zelenka | Pedestrian
(uncredited) |