Cast:
- Keir Dullea as Dr. David Bowman
- Gary Lockwood as Dr. Frank Poole
- William Sylvester as Dr. Heywood R. Floyd
- Douglas Rain as the voice of the HAL 9000
- Daniel Richter as the chief man-ape ("Moon-Watcher" in Clarke's novel)—Richter, a professional street mime, in addition to playing the lead ape was also responsible for choreographing the movements of the other man-apes, who were mostly portrayed by his standing mime troupe.
- Leonard Rossiter as Dr. Andrei Smyslov
- Margaret Tyzack as Elena
- Robert Beatty as Dr. Ralph Halvorsen
- Frank Miller as mission controller
- Edward Bishop as lunar shuttle captain
- Edwina Carroll as Aries stewardess
- Penny Brahms as stewardess
- Heather Downham as stewardess
- Maggie d'Abo as stewardess (Space station elevator)
- Chela Matthison as stewardess (Mrs.Turner, Space station reception)
- Alan Gifford as Poole's father
- Ann Gillis as Poole's mother
- Vivian Kubrick (uncredited) as Floyd's daughter
- Kenneth Kendall (uncredited) as the BBC announcer
