 | Roy Scheider als Dr. Heywood Floyd |
 | John Lithgow als Dr. Walter Curnow |
 | Helen Mirren als Tanya Kirbuk |
 | Bob Balaban als Dr. R. Chandra |
 | Keir Dullea als Dave Bowman |
 | Douglas Rain als HAL 9000 |
 | Madolyn Smith Osborne als Caroline Floyd |
 | Savely Kramarov als Dr. Vladimir Rudenko |
 | Taliesin Jaffe als Christopher Floyd |
 | James McEachin als Victor Milson |
 | Mary Jo Deschanel als Betty Fernandez |
 | Elya Baskin als Maxim Brailovsky |
 | Dana Elcar als Dimitri Moisevitch |
 | Oleg Rudnik als Dr. Vasili Orlov |
 | Natasha Shneider als Irina Yakunina |
 | Vladimir Skomarovsky als Yuri Svetlanov |
 | Victor Steinbach als Nikolaj Ternovsky |
 | Candice Bergen als SAL 9000 |
| Gene McGarr als Commercial Announcer |
| Herta Ware als Jessie Bowman |
| Arthur C. Clarke | Novel |
| Richard L. Anderson | Supervising Sound Editor |
| Rick Simpson | Set Decoration |
| Albert Brenner | Production Design |
| Ralph Gerling | Camera Operator |
| M. James Arnett | Stunt Coordinator |
| Patricia Norris | Costume Design |
| David Shire | Original Music Composer |
| Greg Papalia | Set Designer |
| Michael Westmore | Makeup Supervisor |
| William S. Beasley | First Assistant Director |
| Peter Hyams | Screenplay |
| Peter Hyams | Director |
| Peter Hyams | Director of Photography |
| Peter Hyams | Producer |
| Mario Iscovich | Location Manager |
| Mia Goldman | Editor |
| James Mitchell | Editor |
| Penny Perry | Casting |
| Bruce McBroom | Still Photographer |
| Marshall Schlom | Script Supervisor |
| William Saracino | Music Editor |
| Nancy McArdle | Costume Supervisor |
| Bruce Walkup | Costume Supervisor |
| Gregory L. McMurry | Visual Effects Supervisor |
| Randy Peters | Transportation Coordinator |
| Gregory Pickrell | Set Designer |
| Marty Wunderlich | Property Master |
| Dale Strumpell | Sound Designer |
| Carlos Delarios | Sound Re-Recording Mixer |
| Michael J. Kohut | Sound Re-Recording Mixer |
| Ray O'Reilly | Sound Re-Recording Mixer |
| Aaron Rochin | Sound Re-Recording Mixer |
| John Baron | Chief Lighting Technician |
| Paul Huston | Conceptual Design |
| Vivian McAteer | Hairstylist |
