- Ewan McGregor as Edward Bloom (young)
- Albert Finney as Edward Bloom (senior)
- Perry Walston as Edward Bloom (age 10)
- Billy Crudup as Will Bloom
- Grayson Stone as Will Bloom (age 6–8)
- Jessica Lange as Sandra Bloom (senior)
- Alison Lohman as Sandra Bloom (young), née Templeton
- Helena Bonham Carter as Jenny (young & senior) / The Witch
- Hailey Anne Nelson as Jenny (age 8)
- Robert Guillaume as Dr. Bennett (senior)
- Marion Cotillard as Joséphine
- Missi Pyle as Mildred
- Matthew McGrory as Karl the Giant
- David Denman as Don Price (age 18–22)
- John Lowell as Donald "Don" Price (age 12)
- Loudon Wainwright III as Beamen
- Ada Tai and Arlene Tai as Ping and Jing
- Steve Buscemi as Norther Winslow
- Danny DeVito as Amos Calloway
- Deep Roy as Mr. Soggybottom
- R. Keith Harris as Ed's Father
- Karla Droege as Ed's Mother
- Zachary Gardner as Zacky Price (age 10)
- Darrell Vanterpool as Wilbur (age 10)
- Miley Cyrus[a] as Ruthie (age 8)
- Joseph Humphrey as Little Brave
- Billy Redden as Banjo Man
- Russell Hodgkinson as Some Farmer
- Daniel Wallace as Econ. Professor
- George McArthur as Colossus
- Bevin Kaye as River Woman
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