Wade Wilson (Ryan Reynolds), a.k.a. Deadpool, is depressed. Not only has he been dumped by his girlfriend Vanessa (Morena Baccarin), but he's been rejected by the Avengers and is now selling used cars. That is, until Mr. Paradox (Matthew Macfadyen), an agent for the Time Variance Authority asks Wade to join the Marvel Cinematic Universe to help safeguard the multiverse.

Deadpool's first order of business is to travel to another timeline to team up with Wolverine (Hugh Jackman), who turns out to be more surly and cranky than he expected. They go through a "Void" ruled by Charles Xavier's twin sister Cassandra Nova (Emma Corwin), which is filled with debris from 20th Century Fox films.

Their mission is to save Wade's universe before it's destroyed, along with his friends.