| William H. Macy | Frank Gallagher |
| Emmy Rossum | Fiona Gallagher |
| Justin Chatwin | Steve |
| Ethan Cutkosky | Carl Gallagher |
| Shanola Hampton | Veronica Fisher |
| Steve Howey | Kevin Ball |
| Emma Kenney | Debbie Gallagher |
| Cameron Monaghan | Ian Gallagher |
| Jeremy Allen White | Lip Gallagher |
| Laura Wiggins | Karen Jackson
(as Laura Slade Wiggins) |
| Joan Cusack | Sheila Jackson |
| Dennis Boutsikaris | Professor Hearst |
| Madison Davenport | Ethel |
| Noel Fisher | Mickey Milkovich |
| Chris Gartin | Chip Lishman |
| Jane Levy | Mandy Milkovich |
| Pej Vahdat | Kash |
| Paige Lindsey White | Dr. Seery |
| Corina Boettger | Pimply Girl |
| Timothy George Connolly | Sleazy Guy |
| Katherine Cunningham | Danielle |
| Missy Doty | Jess |
| Sonia Jackson | Darla Martini |
| Brooke Kuchuris | Mom |
| Michael Liu | Hugh |
| Michael Patrick McGill | Tommy |
| Bre Mueck | Beautiful Woman |
| Jeffery Self | Grant |
| Jasmin Tavarez | Gisela |
| Timothy Geithner | Self - U.S. Secretary of the Treasury
(archive footage) (uncredited) |
| Adam Goodell | College Student
(uncredited) |
| Norma J. Houser | Store Patron
(uncredited) |
| Blake Alexander Johnson | Liam Gallagher
(uncredited) |
| Samuel Meadows | College Student
(uncredited) |
| Jay Murray | Store Patron
(uncredited) |