- Keir Dullea as Dr David Bowman
- Gary Lockwood as Dr Frank Poole
- William Sylvester as Dr Heywood Floyd
- Daniel Richter as Moonwatcher, the chief man-ape
- Leonard Rossiter as Dr Andrei Smyslov
- Margaret Tyzack as Elena
- Robert Beatty as Dr Ralph Halvorsen
- Sean Sullivan as Dr Roy Michaels[4]
- Douglas Rain as the voice of HAL 9000
- Frank Miller as mission controller
- Edwina Carroll as lunar shuttle stewardess
- Penny Brahms as stewardess
- Heather Downham as stewardess
- Alan Gifford as Poole's father
- Ann Gillis as Poole's mother
- Maggie d'Abo as stewardess (Space Station 5 elevator) (uncredited)[5]
- Chela Matthison as Mrs. Turner, Space Station 5 reception (uncredited)[6]
- Vivian Kubrick as Floyd's daughter, "Squirt" (uncredited)[7]
- Kenneth Kendall as BBC announcer (uncredited)[8]
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