| Kevin Michael Richardson | | Thadeus |
| Pamela Adlon | | Jue (segment "Final Flight of the Osiris") / Manabu (segment "Beyond") (voice) |
| John DiMaggio | | Crew Man (segment "Final Flight of the Osiris") / Kaiser (segment "Program") (voice) |
| Tom Kenny | | Operator (segment "Final Flight of the Osiris") (voice) |
| Rick Gomez | | Pilot (segment "Final Flight of the Osiris") (voice) |
| Tara Strong | | Crew Woman (segment "Final Flight of the Osiris") / Nurse (segment "World Record") / Misha (segment "Beyond") (voice) |
| Bette Ford | | Old Woman (segment "Final Flight of the Osiris") (voice) |
| Julia Fletcher | | The Instructor (segments "The Second Renaissance, Parts I&II") / Narrator (segment "World Record") / Townsperson (segment "Beyond") (voice) |
| Dane A. Davis | | 01 Versatran Spokesman (segment "The Second Renaissance, Part II") (voice) |
| Debi Derryberry | | Kid (segment "The Second Renaissance, Part II") (voice) |
| Jill Talley | | Mother (segments "The Second Renaissance, Parts I&II") / Townsperson (segment "Beyond") (voice) |
| Dwight Schultz | | Townspeople / Policeman / Exterminators (segment "Beyond") / Nonaka (segment "Matriculated") (segments "The Second Renaissance, Part I & II") (voice) |
| James Arnold Taylor | | Ash (segment "A Detective Story") / Raul (segment "Matriculated") / Miscellaneous Voices (segments "The Second Renaissance, Parts I&II" - "Kid's Story") (voice) |
| Clayton Watson | | Michael Karl 'The Kid' Popper (segment "Kid's Story") (voice) |
| Keanu Reeves | | Neo (segment "Kid's Story") (voice) |
| Carrie-Anne Moss | | Trinity (segments "Kid's Story" and "A Detective Story") (voice) |
| John DeMita | | Teacher (segment "Kid's Story") (voice) |
| Hedy Burress | | Cis (segment "Program") / Yoko (segment "Beyond") (voice) |
| Phil LaMarr | | Duo (segment "Program") (voice) |
| Victor Williams | | Dan (segment "World Record") (voice) |
| John Wesley | | Dan's Dad (segment "World Record") (voice) |
| Alex Fernandez | | Tom (segment "World Record") (voice) |
| Allison Smith | | Reporter (segment "World Record") (voice) |
| Matt McKenzie | | Agent #1 (segment "World Record") / Agent (segments "Beyond" and "A Detective Story") (voice) |
| Tress MacNeille | | Housewife / Kenny (segment "Beyond") (voice) |
| Kath Soucie | | Pudgy / Masa / Sara (segment "Beyond") (voice) |
| Jack Fletcher | | Townsperson (segment "Beyond") / Sandro (segment "Matriculated") (voice) |
| Terrence 'T.C.' Carson | | Clarence (segment "A Detective Story") (voice) |
| Melinda Clarke | | Alexa (segment "Matriculated") (voice) |
| Rodney Saulsberry | | Chyron (segment "Matriculated") (voice) |
| Olivia d'Abo | | Rox (segment "Matriculated") (voice) |
| Bill R. Dean | | (voice) |
| Eric Aten | | Noah, Tyler |