| 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 |
| Tim Bagley | Officer Mike |
| Vanessa Bell Calloway | Carol Fisher |
| Tyler Jacob Moore | Tony Markovich |
| Joel Murray | Eddie Jackson |
| Tyler F. Anderson | Kenny Dombrowski
(as Tyler Anderson) |
| Missy Doty | Jess |
| Rebecca Hall | Newscaster |
| Kate James | Bystander #2 |
| Jes Macallan | Tammy |
| Billy Mayo | Dispatch |
| Virginia Morris | Mrs. Bergdoll |
| Allison Latta | Mrs. Casden |
| William Smillie | Mr. Casden |
| Ben Tedder | Bystander #1 |
| Cheryl Texiera | Tina |
| Rod Blagojevich | Liam's Previous Foster Parent
(archive footage) (uncredited) |
| Blake Alexander Johnson | Liam Gallagher
(uncredited) |
| Blaine Mallory | Angel Girl
(uncredited) |
| Karmen Morales | Tina's Hot Friend
(uncredited) |
| Steven Hugh Nelson | Delivery Man
(uncredited) |
| Sasha Rossof | Pumpkin Girl
(uncredited) |
| Destiny Soria | Lady in red coat
(uncredited) |