Ryan Reynolds as Wade Wilson / Deadpool: A wise-cracking mercenary from Earth-10005 with regenerative healing, but scarring all over his body, and an liaison for the TVA.
Peggy as Dogpool: Wade's deformed Sharpei, and a variant of himself.
Hugh Jackman as Logan / Wolverine: A variant of Wolverine from a universe where let down the inhabitants and slaughtered the humans when they went mutant hunting.
Dafne Keen as Laura Kinney / X-23: A Transigen experiment and Logan's daughter, who has two sets of adamantium claws as well as adamantium claws from her toenails.
Morena Baccarin as Vanessa Carlysle: Wade's fiancée and girlfriend.
Leslie Uggams as Blind Al: Wade's wise, blind, and elderly roommate.
Karan Soni as Dopinder: Wade's admirer and de facto chauffeur.
Stefan Kapicic as Colossus: A member of the X-Men, who can turn his body into solid metal.
Brianna Hildebrand as Negasonic Teenage Warhead: A member of the X-Men and Yukio's girlfriend with the ability to produce solar flares from her body.
Shioli Kutsuna as Yukio: Negasonic's girlfriend and a member of the X-Men.
Lewis Tan as Rusty / Shatterstar: An sword-wielding assassin and member of Wilson's X-Force team.
Rob Delaney as Peter Wisdom / Peterpool: An admirer of Wilson's Deadpool persona and former member of Wilson's X-Force team.
Randall Reeder as Buck: A mercenary and friend of Wilson's.
Jennifer Garner as Elektra Natchios: An assassin and former girlfriend of Matt Murdock / Daredevil and a member of the Others.
Channing Tatum as Remy LeBeau / Gambit: A mutant and member of the Others with the ability to turn any object into an explosive device.
Wesley Snipes as Eric Brooks / Blade: A vampire/human hybrid and member of the Others, who hunted vampire-like beings in his universe.