| 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 |
| Noel Fisher | Mickey Milkovich |
| Joan Cusack | Sheila Jackson |
| Emily Bergl | Sammi Slott |
| Austin Abrams | Henry McNally |
| Morgan Lily | Bonnie |
| Dennis Cockrum | Terry Milkovich |
| Isidora Goreshter | Svetlana |
| James Allen McCune | Matty Baker |
| Nichole Sakura | Amanda |
| Emy Coligado | Wesley Gretsky |
| Alyson Croft | Frank's RN |
| Suzanne Cryer | Cheryl |
| Ian Kahn | Jason |
| Heather McComb | Wendy |
| Aubrey K. Miller | Emily |
| Teresa Ornelas | Ellie |
| Danika Yarosh | Holly Herkimer |
| Time Winters | Doctor |
| Susie Abraham | Seema |
| Greg Ainsworth | Prob & Stats Professor |
| Izabella Alvarez | Sarah |
| Mark Berry | Cop Julius |
| Sam Buchanan | Claire |
| Paul Butler | Chester |
| Vince Cefalu | Cop Lenny |
| Bridgid Coulter | Nurse Franny |
| Nicholette Dixon | Tanesha |
| Brittany Green | Leona |
| Michaela Rose Haas | Hillary |
| Denise Hughes | Officer Scotty |
| Jason Scott Jenkins | Correctional Officer Anthony |
| Michael Klesic | Russian Priest |
| Kellen Michael | Chuck |
| Randy Mulkey | Uncle Ronnie |
| Nicole Pulliam | Correctional Officer Denise |
| Brenden Sims | Liam Gallagher |
| Tyler Jeffrey Smith | Phil Milkovich |
| Tai Urban | Gary |
| Andrew Cole Abrams | Fireworks Boy |
| Robyn Alysa Abrams | Girl on Playground |
| Tristan Jewel Abrams | Girl on Playground |
| Daria Badanina | Russian Hooker |
| Nancy Barcellona | Inmate |
| Seaonna Chanadet | Student |
| Nina Eristavi | Russian Hooker |
| Lisa Kolb | Inmate |
| Claire 'Fluff' Llewellyn | Inmate on Bus |
| Haley Malan | Student |
| Lisa Pevc | Convict |
| Franklin Ruehl | Mr. Jenkins - Cornea Patient |
| John Smutny | Doctor with Brownie |