The Deadpool video game was announced in 2012 at the San Diego comic con, with a teaser trailer. After the convention, on November 27th, 2012. An article appeared written from Deadpool's perspective confirming the game's development and joking that he took over the development of the game.

The scene where Deadpool dances with Death in his apartment is similar to how John Travolta's and Uma Thurman's characters danced in the 1994 movie Pulp Fiction. The scene also includes a subtle joke about a burger with a French sounding name, referencing a famous line from the same movie.

During the development of the game, High Moon Studios announced a contest that would allow the winner to appear in game. The winner was Bill Salina, a Database Administrator from Atlanta, GA. He appears as the character Storm Thrower, who as he is attacked will name off pizzas.

Deadpool had a different costume in the teaser trailer.

During level 3, in the sewers you can find a pizza with a sai stuck into it. This is a reference to the Teenage Mutant Ninja Turtles.

At Deadpool's Surprise Party in Chapter 5, Gambit is playing the keyboard in the far corner. This marks his only actual appearance in the game (not counting all the failed clones based on him).