Ryan Reynolds (Wade Wilson / Deadpool), Morena Baccarin (Vanessa Carlysle), Ed Skrein (Francis Freeman / Ajax), T. J. Miller (Jack 'Weasel' Hammer), Gina Carano (Christina / Angel Dust), Stefan Kapicic (Piotr Rasputin / Colossus), Brianna Hildebrand (Ellie Phimister / Negasonic Teenage Warhead), Leslie Uggams (Blind Al), Jed Rees (Rekrutierer), Karan Soni (Dopinder), Taylor Hickson (Meghan Orlovsky), Rachel Sheen (Weasels Frau), Michael Benyaer (Warlord), Style Dayne (Jeremy), Kyle Cassie (Gavin Merchant), Olesia Shewchuk (Mutter in Guadalajara), Randal Reeder (Buck), Isaac C. Singleton jr. (Boothe), Dan Zachary (Biker), Sean Quan (10jähriger Junge), Justyn Shippelt (Kartenabreißer in der Spielhalle), Donna Yamamoto (Onkologe), Hugh Scott (David Cunningham), Cindy Piper (Händlerin in Chinatown), Emily Haine (tuschelnde Freundin), Aatash Amir (tuschelnder Freund), Chad Riley (Schläger im Billardsalon), Paul Belsito (Boss des Fighclubs)