- Michael McKean as David St. Hubbins
- Christopher Guest as Nigel Tufnel (Tuffy)
- Harry Shearer as Derek Smalls
- Rob Reiner as Marty DiBergi
- Tony Hendra as Ian Faith
- R.J. Parnell, (drummer for Atomic Rooster), as Mick Shrimpton
- June Chadwick as Jeanine Pettibone
- Bruno Kirby as limo driver Tommy Pischedda
- Ed Begley, Jr. as John "Stumpy" Pepys
- Danny Kortchmar as Ronnie Pudding
- Fran Drescher as Bobbi Flekman
- Patrick Macnee as Sir Denis Eton-Hogg
- Julie Payne as mime waitress
- Dana Carvey as mime waiter
- Sandy Helberg as Angelo DiMentibelio
- Zane Buzby as Rolling Stone reporter
- Billy Crystal as Morty the Mime
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- Paul Benedict as Tucker "Smitty" Brown
- Howard Hesseman as Terry Ladd (Duke Fame's Manager)
- Paul Shortino as Duke Fame
- Lara Cody as Duke Fame's groupie
- Andrew J. Lederer as student promoter
- Russ Kunkel as doomed drummer Eric "Stumpy Joe" Childs
- Victory Tischler-Blue as Cindy
- Joyce Hyser as Belinda
- Gloria Gifford as the airport security officer with the security wand
- Paul Shaffer as incompetent promoter Artie Fufkin (Polymer Records)
- Archie Hahn as the room service guy
- Charles Levin as Disc 'n' Dat manager
- Anjelica Huston as Polly Deutsch
- Donald Kendrick as Background Vocalist
- Fred Willard as Air Force Lt Bob Hoekstratton
- Wonderful Smith as Backstage Maintenance Worker
- Michel Wagner as the roadie (who lifts Tufnel back to his feet)
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