| 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 |
| Tyler Jacob Moore | Tony Markovich |
| Joel Murray | Eddie Jackson |
| Ali Dean | Egyptian Man |
| Missy Doty | Jess |
| Robert Goodwin | Randy |
| Brian Hamman | Conrad |
| Peter A Kelly | Cop
(as Pete Kelly) |
| Michael Patrick McGill | Tommy |
| Larry Neumann Jr. | Davey |
| Jeremy Riddle | Kyle |
| Maxie Santillan Jr. | Vagrant |
| Max E. Williams | Canadian Cop
(as Max Williams) |
| Steve Kroft | Self - Correspondent
(archive footage) (uncredited) |
| Yohanni Liman | Pedestrian
(uncredited) |
| Tommy Martin | Neighbor Buying Drugs
(uncredited) |
| J. Craig Venter | Self - Microbiologist
(archive footage) (uncredited) |