Supervillains Harley Quinn, Bloodsport, Peacemaker and a collection of nutty cons at Belle Reve prison join the super-secret, super-shady Task Force X as they are dropped off at the remote, enemy-infused island of Corto Maltese.
| Harley Quinn | Margot Robbie |
| Bloodsport | Idris Elba |
| Peacemaker | John Cena |
| Colonel Rick Flag | Joel Kinnaman |
| King Shark (voice) | Sylvester Stallone |
| Amanda Waller | Viola Davis |
| Polka-Dot Man | David Dastmalchian |
| Ratcatcher 2 | Daniela Melchior |
| Savant | Michael Rooker |
| Captain Boomerang | Jai Courtney |
| Thinker | Peter Capaldi |
| Sol Soria | Alice Braga |
| Blackguard | Pete Davidson |
| Mayor General Mateo Suarez | Joaquín Cosío |
| Presidente General Silvio Luna | Juan Diego Botto |
| Tyla | Storm Reid |
| T.D.K. | Nathan Fillion |
| Ratcatcher | Taika Waititi |
| John Economos / On-Set King Shark | Steve Agee |
| Weasel / Calendar Man | Sean Gunn |
| Doctor Fitzgibbon | John Ostrander |
| Javelin | Flula Borg |
| Mongal | Mayling Ng |
| Briscoe | Stephen Blackehart |
| Flo Crawley | Tinashe Kajese |
| Emilia Harcourt | Jennifer Holland |
| Sliced Dome Soldado | Fernando Martinez |
| Sebastian (voice) | Dee Bradley Baker |
| Kaleidoscope | Natalia Safran |
| Double Down | Jared Leland Gore |
| Teniente | Rey Hernandez |
| Coronel | Ray Benitez |
| Large Guerrilla | Reinaldo Faberlle |
| Delicious Hot Dog Guerrilla | Jonathan Fritschi |
| Astronaut | Josh Ventura |
| General Vera | Gerardo Davila |
| Camila | Mikaela Hoover |
| Polka-Dot Man's Mom | Lynne Ashe |
| Milton | Julio Cesar Ruiz |
| Road Block Soldado | J.R. Adduci |
| Road Block Soldado #3 | Curtis Lyons Jr. |
| Young Cleo | Maya Le Clark |
| La Gatita Presents Traditional Corto Maltese Dancer | Elideusa Gomes Almeida |
| La Gatita Presents Traditional Corto Maltese Dancer | Shanna Kernan |
| La Gatita Presents Traditional Corto Maltese Dancer | Bridget Taylor |
| La Gatita Presents Traditional Corto Maltese Dancer | Monica Rivera |
| La Gatita Waitress | Andrea Andrade |
| Texting Torturer | Giovanni Rodriguez |
| Isabella | Giovannie Cruz |
| Isabella's Second | Sergio Carlo |
| Torn-In-Half Soldado | Edgar Zanabria |
| Security Dispatcher | Grecia Balboa |
| Bespectacled Soldado | Kenneth Trujillo |
| Star-Crossed Man | Randy Havens |
| Star-Crossed Woman | Michelle Civile |
| Star-Crossed Kid | Gabrielle Manning |
| Star-Crossed Dude | Michael Aaron Milligan |
| Star-Crossed Gal | Diany Rodriguez |
| Star-Crossed Lady | Teresita Mans |
| Crew Chief | Terence Rosemore |
| Dancing La Gatita Bar Patron (uncredited) | Lloyd Kaufman |
| La Gatita Amable Dancer (uncredited) | Pom Klementieff |
