Wade Wilson (Ryan Reynolds) is a former Special Forces operative who now works as a mercenary. His world comes crashing down when evil scientist Ajax (Ed Skrein) tortures, disfigures and transforms him into Deadpool.
The rogue experiment leaves Deadpool with accelerated healing powers and a twisted sense of humor. With help from mutant allies Colossus and Negasonic Teenage Warhead (Brianna Hildebrand), Deadpool uses his new skills to hunt down the man who nearly destroyed his life.
Wade Wilson is a former special forces operative who works as a mercenary in New York City. He meets escort Vanessa Carlysle at a local bar and they become romantically attached. One year later, Wade proposes to her and she accepts, but he suddenly collapses. Wade is diagnosed with terminal cancer and though Vanessa remains by his side, he fears losing her.
A recruiter from a secret program approaches Wade offering an experimental cure for his cancer. Although Wade initially refuses, he decides to leave Vanessa and undergo the procedure. At a laboratory, Wade meets Ajax and Angel Dust, whom he instantly resents.
Ajax injects Wade with a serum designed to awaken latent mutant genes, then has him subjected to weeks of torture to induce stress and trigger the mutation without success. Wade discovers Ajax’s real name, Francis Freeman, and mocks him. In response, Ajax straps Wade into an airtight chamber which raises and lowers the oxygen level to keep Wade constantly on the verge of asphyxiation.
Ajax reveals to Wade their true purpose: to make super-powered slaves to be sold to wealthy customers. Several days later, Wade develops a healing factor which cures his cancer and he escapes from the chamber with a severely disfigured face and skin.
He attacks Ajax, but relents when told that his disfigurement can be cured. Ajax subdues Wade, impales him with a rebar and leaves him for dead in the burning laboratory.
Wade attempts to return to Vanessa, but is afraid of her rejecting him because of his appearance and keeps himself away from her. After consulting his best friend Weasel, Wade decides to hunt down Ajax and have his disfigurement cured.
He becomes a masked vigilante, takes the alias “Deadpool”, and moves into the home of an elderly blind woman named Al. Following a string of leads, Deadpool tracks down Ajax to a convoy of cars on an expressway. He kills all the escorts, corners Ajax and demands a cure to his disfigurement.
The confrontation is interrupted by two X-Men, Colossus and Negasonic Teenage Warhead, who have been trying to recruit Deadpool. Taking advantage of the distraction, Ajax escapes. Colossus handcuffs himself to Deadpool and begins dragging him away, in order to take him with them back to the X-Men’s mansion. Deadpool cuts off his own hand and escapes. His hand slowly regenerates overnight.
Ajax goes to Weasel’s bar and learns about Vanessa. In response, Weasel calls Wade and tells him Vanessa is in danger. Wade goes to the strip club where she works but hesitates before he can face her. As a result, Ajax has time to kidnap Vanessa. He and Angel Dust tell Deadpool to meet them on a decommissioned helicarrier in a scrapyard.
Deadpool convinces Colossus and Negasonic to help him, and the trio takes a cab to the scrapyard. While Colossus and Negasonic battle Angel Dust, Deadpool fights his way through Ajax’s henchmen, and eventually engages him in close combat.
After Angel Dust knocks out Colossus, Negasonic uses her power to repel her, but accidentally destroys the equipment holding the helicarrier upright. As the helicarrier tips over, Colossus wakes up and takes Negasonic and Angel Dust to safety, while Deadpool successfully saves Vanessa. Ajax, still alive, attacks Deadpool, but is subdued and reveals there is no cure for Wade’s disfigurement.
Colossus begins urging Deadpool to be a true hero and spare his enemy, but Deadpool kills Ajax. Wade turns to Vanessa, who removes his mask revealing his face. Vanessa is angered that Wade left her, but still loves him. She accepts him, and they reconcile by kissing.