Eddie Brock and the Venom symbiote are drunk in a bar in Mexico,[a] still on the run after their recent battle with Carnage.[b] The murder of Patrick Mulligan makes international headlines with Eddie being named the prime suspect, forcing him to set out to New York City and attempt to clear his name.
Not known to either of them, a creature known as a Xenophage has begun tracking Eddie and Venom. The recent events catch the attention of Rex Strickland, a soldier who oversees Imperium, a government operation at the site of the soon-to-be-decommissioned Area 51 for the capture and study of other symbiotes that have fallen to Earth. Mulligan, revealed to have survived his encounter with Carnage, is captured after being left for dead by another symbiote, who eluded Strickland's soldiers. He is bonded with one of many contained symbiotes and questioned by Imperium researchers Dr. Teddy Payne and Sadie Christmas, to learn about the symbiotes' purpose on Earth before Strickland is ordered to bring Venom down.
While attaching themselves onto the side of an airplane bound for New York City, Eddie and Venom are attacked by the Xenophage tracking them and are forced to drop off into a desert field. Venom explains to Eddie that Xenophages were unleashed into the universe by Knull, the creator of the symbiotes, to retrieve a Codex, which is forged when a symbiote resurrects its host. This can be used to free Knull from the prison the symbiotes trapped him in long ago. Because Venom revived Eddie once before,[c] he now carries a Codex that the Xenophage has now tracked to Earth. After being ambushed by Strickland and his team while barely escaping from them and the Xenophage, Eddie meets Martin Moon and his family of traveling hippie and alien enthusiasts who offer him a free ride to Las Vegas on their way to Area 51. Meanwhile, Mulligan's new symbiote informs Strickland of Knull's intentions with the Codex, which can only be destroyed if either Eddie or Venom dies.
Arriving in Las Vegas, Eddie and Venom run into Mrs. Chen at a casino on vacation and Venom shares a dance with her before being ambushed by the Xenophage again. Strickland's team arrives, separates Venom from Eddie and takes them to Area 51 where Eddie reunites with Mulligan. Sadie frees Venom, who re-bonds with Eddie after Strickland shoots him. This attracts the Xenophage to the base, killing Mulligan. Venom has the other confined symbiotes released, which bond with Sadie and other hosts to fight off the Xenophage, who has signaled to Knull that the Codex has been found. Knull sends more Xenophages through portals to Earth, overwhelming the symbiotes. Realizing he must sacrifice himself to destroy the Codex and save the universe, Venom merges with the Xenophages, leads them into acid tanks, and bids Eddie farewell before ejecting him as a mortally-wounded Strickland sets off his grenades to destroy them. Payne bonds with a symbiote to save Sadie from the explosion while Eddie falls unconscious as the base burns.
Eddie later wakes up in a hospital, where a military official informs Eddie that his actions with Venom at Area 51 have earned him a pardon, under the condition of keeping the events that transpired a secret. Arriving in New York City, Eddie gazes at the Statue of Liberty while remembering Venom.
In a mid-credits scene, Knull declares that the universe is no longer safe from him now that Venom has fallen. In a post-credits scene, a panicked bartender escapes the burned remains of Area 51 as a black cockroach crawls out of the rubble next to a broken vial that previously contained a sample of the Venom symbiote.
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