| 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
(credit only) |
| Noel Fisher | Mickey Milkovich |
| Emma Greenwell | Mandy Milkovich |
| Jake McDorman | Mike Pratt |
| Emily Bergl | Sammi Slott |
| Alex Borstein | Lou Deckner |
| Nick Gehlfuss | Robbie Pratt |
| Dennis Cockrum | Terry Milkovich |
| Isidora Goreshter | Svetlana |
| James Allen McCune | Matty Baker |
| Adam Cagley | Ron Kuzner |
| Michael Patrick McGill | Tommy |
| Kerry O'Malley | Kate |
| Kai Caster | Seth |
| Rosalind Chao | Doctor |
| Svetlana Efremova | Sasha |
| Gideon Emery | Professor Moss |
| Michael Mantell | Dean Wheeler |
| Danika Yarosh | Holly Herkimer |
| Jaime Alvarez | Worker |
| Jocelyn Ayanna | Shonda |
| Sheldon Bailey | Kenyatta
(as Shel Bailey) |
| Greg Bryan | Campus Cop |
| Kelvin Brown | Campus Cop 2 |
| Steven M. Gagnon | Bill Pratt |
| Jim Hoffmaster | Kermit |
| Miguel Izaguirre | Paco |
| Daniel Kash | Russian |
| Lidiya Korotko | Pissed Russian Whore |
| Nikki Segal | Laundry Girl
(as Nicole Segal) |
| Abram Teunissen | Wolf |
| Daria Badanina | Russian Hooker
(uncredited) |
| Mike Cochrane | Alibi Bar Regular
(uncredited) |
| Jeff Dlugolecki | Junkie
(uncredited) |
| Gena Ellis | Commuter
(uncredited) |
| Nina Eristavi | Russian Hooker
(uncredited) |
| Brenden Sims | Liam Gallagher
(uncredited) |
| Cassandra Starr | Russian Hooker
(uncredited) |