| 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 |
| Emily Bergl | Sammi Slott |
| Joan Cusack | Sheila Jackson |
| Dermot Mulroney | Sean Pierce |
| Steve Kazee | Gus Pfender |
| Alessandra Ford Balazs | Jackie Scabello
(as Alessandra Balazs) |
| Nichole Sakura | Amanda
(as Nichole Bloom) |
| Vanessa Bell Calloway | Carol Fisher |
| Isidora Goreshter | Svetlana |
| Dichen Lachman | Angela |
| Axle Whitehead | Davis |
| Adam Cagley | Ron Kuzner |
| Michael Patrick McGill | Tommy |
| Rebecca Metz | Melinda |
| Kellen Michael | Chuckie Slott |
| Mallory Moye | RJ |
| David Storrs | Rinaldo |
| Carlos Ayala | Salty |
| Matthew Boylan | Honey |
| Evan Bruce | Wayne |
| Lynn Chao | Mary |
| Frank Clem | Joe |
| Kate Comer | Art Teacher |
| Jackson A. Dunn | Will |
| Rudy Galvan | Stumpy |
| Kamal Hans | Patel |
| Ileana Huxley | Nika
(as Illeana Huxley) |
| Aaron Kirby | Arnie |
| Erick Lopez | Polo |
| Christopher Michael Moore | Fred |
| Lauren Plaxco | Nicole |
| Brenden Sims | Liam Gallagher |
| Christopher Stills | Chris
(as Chris Stills) |
| J. Michael Trautmann | Iggy Milkovich |
| Tarquin Wilding | Gay Guy |
| Jeff Dlugolecki | Man on Train
(uncredited) |
| Gary W Golden | El Passenger
(uncredited) |
| Christopher Kahler | Nerney
(uncredited) |
| Claire 'Fluff' Llewellyn | Train Passenger
(uncredited) |
| Kris Mardula | College Student
(uncredited) |
| Lisa Pevc | Diner Patron
(uncredited) |
| Donte Phelps | College Student
(uncredited) |
| Elizabeth Reiners | EL Passenger
(uncredited) |
| Frankie Sims | Alibi Bar Patron
(uncredited) |
| Hans Dieter Wolff | Trucker
(uncredited) |