| Name | Character | Episodes |
|---|---|---|
| Linda Cardellini | Lindsay Weir | 18 |
| James Franco | Daniel Desario | 18 |
| Seth Rogen | Ken Miller | 18 |
| John Francis Daley | Sam Weir | 18 |
| Jason Segel | Nick Andopolis | 18 |
| Martin Starr | Bill Haverchuck | 18 |
| Joe Flaherty | Harold Weir | 18 |
| Samm Levine | Neal Schweiber | 18 |
| Busy Philipps | Kim Kelly | 18 |
| Becky Ann Baker | Jean Weir | 18 |
| Steve Bannos | Frank Kowchevski | 12 |
| Sarah Hagan | Millie Kentner | 11 |
| Natasha Melnick | Cindy Sanders | 10 |
| Chauncey Leopardi | Alan White | 9 |
| Dave Allen | Jeff Rosso | 9 |
| Thomas F. Wilson | Coach Ben Fredricks | 6 |
| Trace Beaulieu | Hector Lacovara | 6 |
| JoAnna Garcia Swisher | Vicki Appleby | 5 |
| Riley Smith | Todd Schellinger | 5 |
| Lizzy Caplan | Sara | 4 |
| Sam McMurray | Dr. Vic Schweiber | 3 |
| Kayla Ewell | Maureen Sampson | 3 |
| Joel Hodgson | Discotheque DJ | 3 |
| Jarrett Lennon | Colin | 3 |
| Ron Lester | Seidleman | 3 |
| Matthew McKane | Mike Stevens | 3 |
| Kevin Tighe | Mr. Andopolis | 2 |
| Ann Dowd | Cookie Kelly | 2 |
| Samaire Armstrong | Laurie | 2 |
| Ben Foster | Eli | 2 |
| Claudia Christian | Gloria Haverchuck | 2 |
| Tom Virtue | Mr. Sampson | 2 |
| Amy Aquino | Mrs. Schweiber | 2 |
| Stephanie Erb | Ms. Yeats | 2 |
| Alan Simpson | Tom | 2 |
| Jessica Campbell | Amy Andrews | 2 |
| Ben Stiller | Agent Meara | 1 |
| Shia LaBeouf | Herbert | 1 |
| Alexandra Breckenridge | Shelly Weaver | 1 |
| Matt Czuchry | Teenage Guy #1 | 1 |
| Leslie Mann | Miss Foote | 1 |
| Rashida Jones | Karen Scarfolli | 1 |
| Jason Schwartzman | Howie Gelfand | 1 |
| David Krumholtz | Barry Schweiber | 1 |
| Kenn Michael | Calvin | 1 |
| Kristy Wu | Mousy Girl | 1 |
| Bianca Kajlich | Piercing Girl | 1 |
| Kevin Corrigan | Toby | 1 |
| Mike White | Chip Kelly | 1 |
| Brianna Brown | The Cheerleader | 1 |
| David Koechner | Iron Horse Restaurant Waiter | 1 |
| Meagen Fay | Mrs. Kentner | 1 |
| Jack Conley | Kim Kelly's Stepfather | 1 |
| John Apicella | Dr. Melvin Latz | 1 |
| David Bowe | Salesman | 1 |
| Doug Spinuzza | Frank | 1 |
| Alexander Gould | Ronnie Johnson | 1 |
| Lauren Hodges | Mathlete | 1 |
| Omri Katz | Brad | 1 |
| Paul Feig | Alex the Guitarist | 1 |
| Lyle Kanouse | Auto Shop Manager | 1 |
| Joanna Canton | Cheerleader | 1 |
| Olivia Hack | Erin | 1 |
| Susan Krebs | Housewife | 1 |
| Jeff Judah | Sound Mixer | 1 |
| Bill Chott | Señor O'Hara | 1 |
| Kevin Ruf | Police Officer | 1 |
| Denalda Williams | Angry Mother | 1 |
| Jon Kasdan | Tommy | 1 |
| Tava Smiley | Carol | 1 |
| Percy Daggs III | Mathlete #2 | 1 |
| Shawnee Free Jones | Jenna Zank | 1 |
| Mark Phinney | Drummer #2 (uncredited) | 1 |
| Pamela Gordon | Chain Smoking Woman | 1 |
| Gabe Sachs | Drummer | 1 |
| Harriett S. Miller | Mrs. Whitman | 1 |
| Jason Lansing | Ernie Hahuth - Bully #1 | 1 |
| Joel Madison | Mr. Botwinick | 1 |
| Amy Wheaton | Pretty Girl | 1 |