- Nicolas Cage as Charlie and Donald Kaufman
- Meryl Streep as Susan Orlean
- Chris Cooper as John Laroche
- Cara Seymour as Amelia Kavan
- Brian Cox as Robert McKee
- Tilda Swinton as Valerie Thomas
- Ron Livingston as Marty Bowen
- Maggie Gyllenhaal as Caroline Cunningham
- Judy Greer as Alice
- Bob Yerkes as Charles Darwin
- Jim Beaver as Ranger Tony
- Litefoot as Russell
- Jay Tavare as Matthew Osceola
- Doug Jones as Augustus Margary
- Peter Jason as Defense Attorney
- Gary Farmer as Buster Baxley
Tom Hanks was originally set for the double role of Charlie and Donald Kaufman. Cage took the role for a $5 million salary,[4] and wore a fatsuit during filming.[5]
Streep expressed strong interest in the role of Susan Orlean before being cast,[4] and took a salary cut in recognition of the film's budget.[6] John Turturro was approached to portray John Laroche.[7] Cooper strongly considered turning down Laroche, but accepted it after his wife urged him to.[8] Albert Finney, Christopher Plummer, Terence Stamp and Michael Caine were considered for the role of Robert McKee, but McKee personally suggested Brian Cox to filmmakers.[9]
John Cusack, Catherine Keener, John Malkovich, Lance Acord, Thomas Patrick Smith, and Spike Jonze have uncredited cameos as themselves in scenes where Charlie Kaufman is on the set of Being John Malkovich, which he also wrote. Additional cameos include director Curtis Hanson as Orlean's husband, and David O. Russell as a New Yorker journalist.
