In 2018, Wade Wilson, also known as Deadpool, attempts to join the Avengers by meeting with Happy Hogan. Desperate to find a meaningful purpose for his abilities, Wade is disappointed when Hogan rejects him, citing his poor teamwork skills. Hogan emphasizes that being an Avenger is about being needed by others, not the other way around. Dejected, Wade quits his life as Deadpool and becomes a car salesman at Drive Max, while his girlfriend Vanessa Carlysle breaks up with him.
Six years later, Wade’s friends throw him a birthday party, but the celebration is interrupted by agents from the Time Variance Authority (TVA), who capture him. At the TVA office, Mr. Paradox offers Wade a place on the Sacred Timeline with the Avengers. Excited about joining the Marvel Cinematic Universe (MCU), Wade suits up as Deadpool again. However, Paradox reveals that Wade’s universe is dying because it lost its anchor, Wolverine, who died protecting X-23. Paradox, dissatisfied with the TVA’s leadership, plans to accelerate the destruction of Wade’s universe using the Time Ripper.
Determined to save his home and friends, Deadpool steals a TemPad and searches for Wolverine variants across the multiverse. After many failed attempts, he finds a suitable Wolverine variant in a Canadian bar. This Wolverine, initially uninterested, gets too drunk to resist and passes out. Deadpool brings him to the TVA, but Paradox mocks him for bringing the worst Wolverine variant.
Deadpool discovers that Paradox is acting without TVA authorization, but both he and Wolverine are pruned and sent to the Void. There, Wolverine attacks Deadpool until he convinces him that they can change his past if they return to the TVA. They encounter Johnny Storm, the Human Torch (Deadpool mistakes him for Captain America), and a group of scavengers led by Sabretooth. After a skirmish, they are captured and taken to a base inside the giant corpse of Ant-Man.
At the base, they meet Cassandra Nova, Charles Xavier’s twin sister, who was banished to the Void by the TVA. Nova kills Storm and incapacitates Wolverine, then invades Deadpool’s mind, taunting him with his insecurities. Deadpool and Wolverine recover and attack Nova, but she easily overpowers them and leaves them to be devoured by Alioth. They manage to escape and decide to find the Resistance that Storm mentioned.
On their journey, they meet two Deadpool variants, Dogpool and Nicepool, who help them reach the Void’s borderlands. During the trip, Deadpool admits he isn’t sure the TVA will fix Wolverine’s reality, angering Wolverine. They fight until they are too exhausted and are driven to the Resistance Hideout by an unknown driver.
At the hideout, they meet variants of Elektra, Blade, and Gambit, led by X-23. Deadpool convinces the Resistance to team up against Nova, omitting the true reason for Storm’s death. Wolverine initially refuses to join, but X-23’s words of encouragement change his mind.
X-23 tells Wolverine that she doesn’t need his help but wants him to know she’s proud of him. Wolverine confesses that he abandoned his fellow X-Men in his universe, leading to their deaths at the hands of anti-mutant vigilantes. This guilt drives him to keep wearing his X-Man yellow suit. X-23 reassures him that despite his self-doubt, he remains a good person at heart.
Meanwhile, Pyro tracks Deadpool and Wolverine, striking a deal with Paradox, who decides that Cassandra Nova is too dangerous and must be eliminated. With Wolverine now on their side, the Resistance launches an assault on Nova’s base, aiming to use Juggernaut’s helmet to neutralize her psychic powers. Nova knocks out Deadpool and subdues Wolverine, trying to manipulate him into embracing his primal instincts. Wolverine resists, and Deadpool, with X-23’s help, places Juggernaut’s helmet on Nova, rendering her powerless.
Suddenly, Pyro shoots Nova, and Wolverine urges Deadpool to save her, believing that Charles Xavier would never want her to die. Deadpool complies, and Nova, relenting, uses a Sling Ring with the Reality and Time Stones to open a portal out of the Void, allowing them to escape just before Alioth devours the base. Nova forces Pyro to confess that he acted on Paradox’s orders.
Deadpool and Wolverine reach Earth-10005, where Paradox is preparing the Time Ripper. Nova follows, killing Pyro and revealing her plan to turn the entire Multiverse into the Void. She captures Paradox and sends the Deadpool Corps to stop Deadpool and Wolverine. They battle through the Deadpool variants, who cease fighting upon seeing Peter Wisdom, beloved by all Deadpools.
Reaching Paradox, they learn that Nova has taken control of the Time Ripper and plans to unravel the Multiverse. The only way to stop her is to short-circuit the device’s matter and anti-matter chambers, a task likely to kill them. Wolverine insists on doing it, feeling he has nothing left to fight for, but Deadpool locks him out and prepares to sacrifice himself. Wolverine breaks in and joins him, resulting in the Time Ripper’s destruction and Nova’s death.
B-15 and the TVA arrive to investigate. Paradox, now in custody, blames Nova for the chaos. Deadpool and Wolverine survive by sharing the energy burst. Deadpool asks B-15 to help their Resistance allies in the Void and fix Wolverine’s reality. B-15 agrees to consider it, noting that Wolverine’s tragic past led him to save the Multiverse.
Wilson and Logan reunite with Dogpool over shawarma, mourning Nicepool’s death. They return to Wilson’s place with Blind Al, inviting friends and X-23 to join them. Wilson rekindles his relationship with Vanessa Carlysle.
In a post-credits scene, Deadpool reveals footage proving that Storm did curse out Nova, vindicating his earlier claims.