Wade Wilson launches a daring ambush against Ajax along with his crew on a bustling expressway. This tense skirmish reveals the backstory of how Wade became the infamous Deadpool. Two years earlier, Wade Wilson, portrayed by Ryan Reynolds, is a former special forces operative turned mercenary operating out of New York City. After his dishonorable discharge from the Canadian forces, he crosses paths with the charming escort Vanessa Carlysle, played by Morena Baccarin, at a bar owned by his witty friend Weasel. The two bond over shared experiences of difficult childhoods, igniting a romantic connection that deepens over time.
As their relationship flourishes, Wade lovingly hires Vanessa for a night out at a fair, and they share an intimate evening. One year later, Wade proposes to Vanessa, who happily accepts. However, their blissful moment is shattered when Wade suddenly collapses and receives a devastating diagnosis: terminal lung cancer. Even though Vanessa vows to support him through thick and thin, Wade decides that he cannot bear to watch her suffer as he dies.
Enter a mysterious recruiter, played by Jed Rees, who approaches Wade with an enticing offer — an experimental treatment that could grant him extraordinary powers and a chance at life. Although he is initially reluctant, Wade ultimately chooses to undertake the procedure, leaving Vanessa behind in the process. Inside a shadowy laboratory, he encounters Ajax, played by Ed Skrein, and the imposing Angel Dust, portrayed by Gina Carano, although he quickly grows to despise them both.
Within the lab, Wade witnesses other terminal patients undergoing horrific experiments. Ajax discloses the true nature of their situation: they are part of a sinister plan to create super-powered slaves to be sold off to the highest bidder. Following numerous brutal tortures designed to trigger his latent mutant genes, Wade eventually develops a healing factor that cures his cancer but leaves him horrifically disfigured, his body marred with tumor-like scars.
In a climactic escape attempt, Wade confronts Ajax but is left for dead after a brutal attack. Miraculously, he survives due to his newfound abilities, but now he wrestles with the emotional turmoil of returning to Vanessa, fearing that his grotesque appearance would push her away. Consulting with his loyal friend Weasel, played by T.J. Miller, Wade resolves to hunt down Ajax to reclaim his former self.
Adopting the moniker of "Deadpool," a name birthed from a darkly humorous game of bets in Weasel's bar, he dons a striking red costume suggested by an elderly blind woman named Blind Al. This color choice not only serves practicality but also reflects Deadpool's irreverent personality. Over the course of the year, he interrogates and eliminates various associates of Ajax in a relentless pursuit for revenge.
His quest eventually leads him to a bustling expressway where Ajax is spotted. Accompanied by Dopinder, a cab driver who becomes an unexpected ally, Deadpool engages Ajax's escort before a surprise escalation occurs with the arrival of two X-Men, Colossus and Negasonic Teenage Warhead. Despite their attempts to recruit him, Deadpool remains unyielding, leading to chaos as Ajax seizes the opportunity to escape.
Upon discovering that Vanessa has been kidnapped, Wade's resolve intensifies. He recruits Colossus and Negasonic to assist him in rescuing her from Ajax’s clutches. The final showdown takes place on a decommissioned Helicarrier amidst a fierce battle where Deadpool fights tooth and nail to save Vanessa.
In a moment of brutal confrontation, Deadpool learns a shocking truth: there is no cure for his disfigurement. Yet, in a fit of rage, he ends Ajax's life, only to face Vanessa's wrath when she discovers the truth of Wade’s absence. However, resolution comes when Vanessa surprises Wade with her understanding of his struggle, choosing to reconnect despite his altered appearance.
In a humorous post-credits scene, Wade cheekily addresses the audience, teasing the possibility of a sequel featuring the character Cable.
