Trama

In 2018, Wade Wilson / Deadpool (Ryan Reynolds) is a wisecracking mercenary from Earth-10005 with accelerated healing but severe scarring over his body after undergoing an experimental regenerative mutation to treat terminal cancer.

Wade uses Cable's time-travel device to prevent the death of his girlfriend, Vanessa Carlysle (Morena Baccarin). He then travels from his universe, Earth-10005, to Earth-616, also called the "Sacred Timeline", hoping to join that reality's Avengers. He is rejected by Happy Hogan (Jon Favreau) and returns to his own universe.

Six years later, Wade has broken up with Vanessa, retired from being the masked mercenary Deadpool, and works as a used-car salesman with his friend and former X-Force member Peter Wisdom (Rob Delaney). Wade lives with Blind Al (Leslie Uggams) his elderly roommate. Hi friends include Dopinder (Karan Soni) a taxi driver and admirer of Wade, Negasonic Teenage Warhead (Brianna Hildebrand) a teenage member of the X-Men with the mutant power to detonate atomic bursts from her body, Yukio (Shioli Kutsuna) Negasonic Teenage Warhead's girlfriend, Piotr Rasputin / Colossus (Stefan Kapicic), Buck (Randal Reeder), Rusty / Shatterstar (Lewis Tan) and others.

During Wade's birthday party, he is detained by the Time Variance Authority (TVA) and brought to Mr. Paradox (Matthew Macfadyen), who explains that they are an organization outside of time that monitors the Sacred Timeline and the wider multiverse. He offers Wade a future on the Sacred Timeline which Wade accepts, until Paradox reveals that Wade's universe is deteriorating as a result of the death of its stabilizing "anchor being", Logan / Wolverine (Hugh Jackman) a mutant and former member of the X-Men with healing abilities, retractable claws, and an Adamantium-infused skeleton.

Paradox plans to use a "Time Ripper" device to accelerate this process. In his words he wants to give Earth-10005 a swift and compassionate end. Wade steals Paradox's TemPad device and uses it to travel to Logan's grave, hoping to resurrect him and save their time-line. But even after digging out his skeleton, Wade is not able to bring Logan back. He instead uses Logan's bones to fight off the TVA agents sent by Paradox. The TemPad device opens portals to other Universes at will and Wade can travel seamlessly to them. Wade then travels the multiverse searching for a replacement "variant" of Logan.

Wade returns to the TVA with a variant of Logan. Paradox says an anchor being cannot be replaced, especially by this variant who is considered to be the worst Wolverine in the multiverse. Paradox says that this particular Wolverine let down his entire world, in an act that was beyond forgiveness.

When Wade deduces that Paradox is acting without the knowledge of his superiors, Paradox sends Wade and Logan to the Void, a wasteland at the end of time. Wade and Logan end up fighting each other but eventually realize that neither of them can be killed by conventional means.

Wade claims the TVA can change events in Logan's past, convincing him to work together to escape the Void. The pair are captured alongside Johnny Storm / Human Torch (Chris Evans) a member of the Fantastic Four who can engulf himself in and control fire, and fly, and taken to Cassandra Nova (Emma Corrin), the powerful and sadistic twin sister of X-Men leader Charles Xavier, and a mutant with Telekinetic and Telepathic powers. Cassandra, who made a deal with the TVA to oversee the Void. Cassandra was sent to the void in exchange for the ability to walk.

Wade jokes about how Johnny said insulting things about Cassandra on the way over. Cassandra kills Johnny and leaves Wade and Logan to be consumed by the creature Alioth, but the pair escape using a jet pack in Cassandra's compound. Wade and Logan find an abandoned diner in the void and eat whatever they can find as they share their insecurities with each other. Wade says that in his world, Wolverine died trying to save the X-23, a clone that they raised in a lab.

Logan and Wade meet a Deadpool variant called "Nicepool" who directs them towards a resistance group that has been fighting Cassandra. Wade accidentally admits that he is not certain whether the TVA can change Logan's time-line, and the pair fight until they are both unconscious. Logan is livid with Wade and says that it is not a surprise that Wade was rejected by the Avengers and the X-Men, who pretty much take everyone.

They are found by the resistance group, consisting of Laura / X-23 (Dafne Keen) a female clone of Logan, Elektra (Jennifer Garner) a skilled fighter who uses a pair of Sai weapons, Blade (Wesley Snipes) the half-vampire "Daywalker", and Gambit (Channing Tatum). The superheroes were sent to the void when their own world's were destroyed due to the end of their Anchor Beings.

Wade proposes an alliance and Laura convinces Logan, regretful of his past actions which led to the deaths of his fellow X-Men, to join. The plan is to storm Cassandra's lair, distract her and find a way back to their Universes.

The resistance members distract Cassandra's henchmen while Wade and Logan block her powers using Juggernaut's (Aaron W. Reed) helmet (which was removed by Laura who defeated Juggernaut and provided the helmet to Wade, as Cassandra was inside Logan's mind). Cassandra says that she cannot send anyone back until the helmet is removed and promises to kill them if they do remove the helmet.

Cassandra is betrayed by her follower John Allerdyce / Pyro (Aaron Stanford) a Pyrokinetic mutant, on behalf of Paradox and almost dies when Pyro shoots her. Turns out Paradox was paying Pyro to take out Cassandra as she was becoming a bigger threat than what Paradox could handle. The only way to save her is to take the helmet off, and Logan convinces Wade to do the same, without any guarantees that Cassandra would not kill them. Cassandra heals herself and uses a Sling Ring to open a portal to Earth-10005 for Logan and Wade.

Cassandra learns about the Time Ripper from Pyro, kills him, and follows Logan and Wade to Earth-10005. She plans to use the Time Ripper to destroy all time-lines, leaving only the Void. Cassandra summons an army of Deadpool variants, who kill Nicepool and battle Wade and Logan until Peter, Wade's friend, arrives to distract them.

Paradox tells Wade and Logan that one of them could destroy the Time Ripper by disrupting its power flow which is comprised of matter and anti-matter flowing into it. But disrupting the flow of matter and anti-matter would bring the 2 entities together and create an explosion that would kill them. Wade and Logan destroy the Time Ripper together, killing Cassandra in the process, and survive by sharing the burden. Paradox is arrested by the TVA's boss Hunter B-15 (Wunmi Mosaku), who congratulates Wade and Logan and says their actions have stopped Earth-10005 from deteriorating.

Wade asks Hunter B-15 to save the resistance group from the Void and change the history of Logan's world. She explains that the latter is not possible because Logan's history is what led to him being a hero now, but allows Logan to stay in Wade's universe. During a gathering with Wade's friends that includes a rescued Laura, Logan encourages Wade to reconcile with Vanessa.