The film starts with Wade Wilson/Deadpool (Ryan Reynolds) arriving at the burial site of Logan/Wolverine (Hugh Jackman) in North Dakota. Deadpool is pissed to find that Logan really is dead and all that’s left of him is his adamantium skeleton. Soon, a team of agents from the Time Variance Authority arrive for Wade. He proceeds to take Logan’s skeleton and slaughters the agents (to the tune of N*Sync) before donning the dearly departed hero’s signature claws.
Wade takes us back to what brought him here, beginning in 2018. Wanting to really apply himself as a true hero for Vanessa (Morena Baccarin), Wade uses Cable’s time-traveling device and goes for an interview in Earth-616 with Happy Hogan (Jon Favreau) to be an Avenger. Happy doesn’t see the potential in Wade, who also isn’t helping by being his usual childish self. He returns to his main universe and gets a job with Peter (Rob Delaney) working at a car dealership over the last six years and retiring his life as Deadpool.
Wade and Peter return to the former’s apartment for a birthday party attended by all of Wade’s closest friends – Vanessa, Blind Al (Leslie Uggams), Dopinder (Karan Soni), Negasonic (Brianna Hildebrand), Yukio (Shioli Kutsuna), Colossus (Stefan Kapicic), Shatterstar (Lewis Tan), and Buck (Randall Reeder). While everyone is having a good time, it is revealed that Wade and Vanessa have been long broken up and seeing other people. Outside, Wade hears a knocking and is met by the TVA agents. He mistakes them for strippers and tries to make fun of them, but they pull him through their portal.
Wade wakes up to meet a TVA agent named Paradox (Matthew Macfadyen). After learning what the TVA does, Wade thinks he’s there because he screwed around with Cable’s device too much, but Paradox says it has nothing to do with that. He brings Wade to a room where he gives Wade an official offer to join Earth-616 (Wade knows he means the MCU). Thinking it will finally give him the purpose and potential to save the world, Wade accepts and dons a new Deadpool suit (and also because one future sees Thor crying over a dying Deadpool). However, he learns from Paradox that the reason he is being sent to a new universe is because the “anchor being” of his universe (the one keeping the universe from falling apart) is dead, and that would be Logan. Wade’s universe will be pruned as a result, and all of his loved ones will go with it. Deadpool then headbutts Paradox in the face and steals his universe-jumping device to find a new Logan.
Deadpool jumps through several universes to find a new Logan. He finds a comics-accurate short one, one with the yellow and brown suit, and even one played by Henry Cavill (Wade ALMOST knocks DC there), but they all claw him apart. He eventually finds one Logan at a bar, drinking his life away. After he passes out, Wade brings him back to the TVA, but Paradox tells him that not only will this not fix anything, but this Wolverine happens to be the worst one across all the timelines, as he is responsible for the downfall of his own universe. Wade and Logan also learn that Paradox and the agents in the room are working separate from the rest of the TVA. When Wade plans on revealing this, Paradox prunes both him and Logan.
The two wake up in The Void, where they violently duke it out. Wade shoots Logan while Logan claws Wade everywhere (mostly his balls) before they cool off and decide to work together to save Wade’s universe and restore Logan’s. They are then found by a mysterious outlander (Chris Evans) just before a group of mutant villains led by Pyro (Aaron Stanford) show up. Wade recognizes the outsider, thinking it’s Captain America and getting excited to hear him say “Avengers, assemble!” But the outsider instead says “Flame on!”, meaning he is JOHNNY STORM! He goes full Human Torch, only for Pyro to drain his fire powers. Wolverine’s old nemesis Sabretooth (Tyler Mane) shows up for a long-awaited rematch, but Logan cuts through his neck like butter. The other mutants capture Wade, Logan, and Johnny.
The villains bring the heroes to the fortress of Cassandra Nova (Emma Corrin), the psychotic twin sister of Charles Xavier who rules inside the giant skeleton of Ant-Man. Among her other minions are Juggernaut, Toad, Psylocke, and Azazel. To show she means business, Cassandra uses her powers to skin Johnny alive and keep him standing consciously long enough before collapsing into a pile of blood and bones. She is also able to use her powers to literally dig her hands into Wade and Logan’s brains to see into their memories, including how Wade and Vanessa broke up. The two are also unable to kill her with their weapons, and Cassandra prepares to leave them to be consumed by Alioth. Wade and Logan use the chaos as an opportunity to find a rocket leg that flies them away to safety.
The two crash-land somewhere and find a rundown diner to get whatever they can find to eat. Wade tries to figure out what’s going on with Logan’s situation, since he was so highly-regarded as the face of the X-Men in Wade’s universe, but Logan won’t say more. Afterwards, the two come upon a small dog with a long tongue called Mary Puppins, AKA “Dogpool”. Wade immediately falls in love with her and then meets a Deadpool variant named “Nicepool”, who is the friendliest Deadpool and also the only one that doesn’t need to wear a mask because he’s still handsome. He warns Wade and Logan about the Deadpool Corps will try to find them and kill them.
Nicepool provides Wade and Logan with a minivan to drive away to the borderlands so they can get back home. On their way, Wade accidentally lets it slip that he lied to Logan about the TVA being able to fix what went wrong in his universe. Logan chews Wade out for lying and says he will never be able to save any world since he couldn’t even save his relationship with Vanessa. They get into another violent fight that lasts until they are both passed out.
An unseen figure takes the minivan with Wade and Logan still passed out. They find themselves in a hidden base belonging to resistance fighters. Wade and Logan then meet (drumroll, please) ELEKTRA NATCHIOS (Jennifer Garner), BLADE (Wesley Snipes), and the never before seen Remy LaBeau, AKA…GAMBIT (Channing Tatum)! The two then meet the leader of the resistance…Laura Kinney (Dafne Keen), who recognizes Logan as a variant of the man who was her father. They were victims of the Void and had many other friends killed by Cassandra (Daredevil, the 2005 Fantastic Four, Quicksilver, among others). They want to take on Cassandra, but Logan is not willing to join the fight.
Laura later finds Logan sitting by a campfire and drinking Gambit’s liquor. He finally explains what happened in his universe, and why he never takes off the iconic yellow and blue suit. All of the X-Men in his universe wanted him to join them, but he refused. After a night out drinking, he came back to the mansion to find that they were all murdered. In his rage, he went on a killing spree where even innocent people got caught in the crossfire, and he wears the suit because it’s all he has left of his friends. Laura says that he is the same as her own Logan was, but that he will be the right guy when it is necessary. He then has a change of heart and agrees to help take down Cassandra
Back on the outskirts on the Void, Pyro contacts Paradox since the two are in cahoots. Paradox is planning to activate something called the Time Ripper, which will quickly prune Wade’s universe faster than it is supposed to be destroyed. He orders Pyro to find Wade, Logan, and the other outsiders before they screw up his plans.
The heroes lead an assault on Cassandra’s base after Blade blows the doors open with one of Punisher’s bazookas. Wade and Logan go after Cassandra while the others try to get Juggernaut’s helmet so that it can be used to block Cassandra’s powers. Elektra, Blade, Gambit, and Laura battle the evil mutants. Blade manages to kill Toad while Gambit uses his cards to blow up some goons, and Laura cuts off Juggernaut’s feet before taking his head. Wade and Logan make it to Cassandra, but she incapacitates both of them. She gets inside Logan’s mind and tries to convince him to let her kill him to make the pain of losing his friends go away. Laura delivers the helmet in time for Wade to plop it onto Cassandra’s head, subduing her powers. However, she tells them that if they kill her, they have no way of going home, and if they take the helmet off, she’s going to kill them anyway. Logan tries to appeal to Cassandra over how much Charles cared about him and humanity, as well as mutantkind. Pyro shows up to shoot Cassandra and kill her himself, but Logan knocks him unconscious. After letting Cassandra go, she uses Doctor Strange’s sling ring (she killed one of his variants) and opens a portal for Wade and Logan to go through before Alioth shows up. The other heroes watch as the two jump through, while Cassandra learns from Pyro what he and Paradox are plotting.
Wade and Logan return to the former’s universe, where Paradox steps out to confront them, but Cassandra emerges from her sling ring portal, along with Pyro (whose neck she breaks). After sticking her hand in Paradox’s head, she has him guide her to the Time Ripper’s location so that she can destroy every single universe until all that is left is the Void. Before the heroes can stop them, they are found by Dogpool and Nicepool, right before the rest of the Deadpool Corps shows up. Led by Lady Deadpool (Blake Lively), plus variants like Kidpool, Babypool, Cowboy Deadpool (Matthew McConaughey), a floating skull head Deadpool (Nathan Filion), and a samurai Deadpool. Wade uses Nicepool as a human shield to get his guns, and Nicepool dies since he’s the only variant that cannot regenerate. Logan then pulls his mask over his head for the first time so that he and Wade can finally team up as DEADPOOL AND WOLVERINE! They proceed to mow down the Deadpools (to the tune of Madonna) before none other than Peter (dressed as Peterpool) shows up to say that Wade is with him, and the Deadpool Corps back off because they all have a Peter in their universe.
Cassandra begins to activate the Time Ripper, just as Hunter B-15 (Wunmi Mosaku) learns of Paradox’s crimes. Deadpool and Wolverine enter the base and learn from Paradox that in order for the Time Ripper to be shut down, they need to disrupt the power flow of the matter and antimatter, but it will kill whoever does it. Wade and Logan argue over who sacrifices themselves, and Wade tries to lock Logan out so he can do it himself. He is only able to grab one cable as Cassandra starts to drain the timelines, but Logan manages to burst through and grab Wade’s hand so that they can use their bodies as conductors. The energy overloads the Time Ripper, destroying it and obliterating Cassandra.
B-15 shows up to confront Paradox, who tries to weasel his way out of punishment before Wade and Logan show up, completely alive. B-15 has Paradox arrested before discovering that Wade and Logan’s actions have fixed Wade’s universe. Wade asks B-15 if they can return the other heroes in the Void, as well as fix Logan’s universe. While she says they can bring back the others, B-15 notes that Logan’s tragedy made him the hero that he is and that there is nothing that needs to be fixed. She bids them farewell, and Wade and Logan go grab food.
Logan prepares to go off by himself, but Wade invites him to remain part of his universe. They are later seen joined by Wade’s friends, plus Laura, and Wade and Vanessa appear to give their relationship another chance.
Mid-Credits Scene: Behind-the-scenes footage of all the old Fox Marvel films (the original X-Men films, the Fantastic Four (2005 and 2015 versions), Daredevil, and Elektra) is played as a tribute.
After-Credits Scene: Deadpool is at the TVA to show footage of Johnny trash-talking Cassandra to prove that he said all of those things that Deadpool repeated, which is what got Johnny killed.
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