| Name | Character | Episodes |
|---|---|---|
| Peter Serafinowicz | The Tick | 22 |
| Valorie Curry | Dot Everest | 22 |
| Yara Martinez | Miss Lint | 22 |
| Brendan Hines | Superian | 22 |
| Griffin Newman | Arthur Everest | 22 |
| Alan Tudyk | Dangerboat (voice) | 17 |
| Devin Ratray | Tinfoil Kevin | 15 |
| Jackie Earle Haley | The Terror | 12 |
| Patricia Kalember | Joan | 11 |
| François Chau | Walter | 10 |
| Marc Kudisch | Ty Rathbone | 7 |
| Steven Ogg | Flexon | 6 |
| Julian Cihi | Edgelord | 6 |
| Michael Cerveris | Ramses IV | 5 |
| Tyler Bunch | Stosh | 5 |
| John Hodgman | Hobbes | 5 |
| Teodorina Bello | Ouma | 5 |
| Liz Vassey | Lobstercules (voice) | 4 |
| Bryan Greenberg | Derek | 4 |
| Happy Anderson | Donny | 4 |
| Townsend Coleman | Midnight (voice) | 4 |
| Clé Bennett | Sage | 4 |
| Clara Wong | Veranda / Miranda | 3 |
| Nick Westrate | Garrett Sinclair | 3 |
| Juliet Adair Pritner | General Julie McGinnis | 3 |
| Malachi Weir | Thug #2 | 2 |
| Michelle Buteau | Beck | 2 |
| Hunter Emery | Danny | 2 |
| Kyle Catlett | Young Arthur | 2 |
| Brian Faherty | Denny | 2 |
| Whoopi Goldberg | Whoopi Goldberg | 1 |
| Berto Colon | Thug #1 | 1 |
| David H. Holmes | Shifty Man | 1 |
| Thomas Kopache | Nabokov | 1 |
| John Cenatiempo | Thug #3 (uncredited) | 1 |
| Christian Navarro | Sidekick | 1 |
| Geoffrey Cantor | Agent Adams | 1 |
| Joanna Adler | Dr. Creek | 1 |
| Joe Holt | Det. Green | 1 |
| Michael McFadden | Thug #3 | 1 |
| Jayne Houdyshell | Black Market Bob | 1 |
| Anthony Alessandro | Romeo | 1 |
| Helen Coxe | Photographer (uncredited) | 1 |
| Helen Coxe | Photographer | 1 |
| Erik Heger | Michael King | 1 |
| Rich Pecci | Police Officer #2 | 1 |
| Ken Marks | Supervisor | 1 |
| Ken Marks | Manager | 1 |
| Mimi Gianopulos | Nikki | 1 |
| Adam Harrington | 1960s News Anchor | 1 |
| Ava Lee Scott | Young Woman | 1 |
| Shadoe Stevens | Narrator (voice) | 1 |
| Marko Caka | Parent (uncredited) | 1 |