During a stormy night on the island of Isla Nublar – the site of the Jurassic World theme park that was abandoned three years earlier – a mercenary team uses a small submarine to retrieve DNA from the deceased hybrid dinosaur Indominus rex, whose remains are in the park’s Mosasaurus lagoon. The Mosasaurus destroys the submarine after it sends the DNA sample to the surface, and the remaining mercenaries evacuate with the DNA when the park’s Tyrannosaurus arrives, consequently leaving the lagoon gate open for the Mosasaurus to escape into the ocean.
On the mainland, there is a debate on whether Isla Nublar’s dinosaurs should be saved from the island’s volcano, which is about to erupt. During a U.S. Senate hearing, Dr. Ian Malcolm states that the dinosaurs should be left to die, as he believes that cloning them was a mistake and that nature is correcting the mistake. Former park manager Claire Dearing has created the Dinosaur Protection Group to save the creatures, along with Franklin, a former park technician, and Zia, a paleo-veterinarian. However, with the Senate decision to reject rescue of the dinosaurs, Claire’s mission is over until she is contacted by Benjamin Lockwood, John Hammond’s partner in creating the cloning technology, until Lockwood split with Hammond.
At Lockwood’s estate in northern California, Claire meets Eli Mills, an aide who has been running Lockwood’s operations. Claire also meets Lockwood’s granddaughter Maisie, who he adopted after her parents died in a car accident. Benjamin wants to proceed with a secret rescue mission to send the dinosaurs to a new island sanctuary where they will live without human interference. Mills is concerned that locating Blue, the last living Velociraptor, will be difficult. Mills convinces Claire to recruit Owen Grady, the park’s Velociraptor researcher, so he can find Blue, who he raised from birth. Owen is reluctant to return to the island, but ultimately agrees after watching video footage of Blue when she was a young raptor.
The rescue group, led by a mercenary named Wheatley, arrives on Isla Nublar. Claire and Franklin stay in an island facility and use their skills to reactivate the park’s trackers to locate dinosaurs, while Owen and the rest of the team search for Blue in the jungle. Upon finding Blue, Wheatley’s mercenaries take her and Zia, while Owen is tranquilized by them and left to die. Claire and Franklin survive a Baryonyx attack and escape the facility. Owen reunites with them as the volcano erupts, which causes a dinosaur stampede. Claire and Franklin use a ball-shaped Jurassic World Gyrosphere ride to flee the stampede and the eruption, but the ride plummets off a cliff and into the ocean. Owen rescues Claire and Franklin, and they wind up on a beach, where Claire realizes that the trio were only used to locate the dinosaurs for a nefarious scheme. At the nearby dock, the captured dinosaurs are loaded onto a ship. Owen, Claire and Franklin sneak aboard and reunite with Zia, and the ship departs as Isla Nublar is destroyed by the volcano.
At Lockwood’s estate, Maisie learns that Mills is working with Gunnar Eversoll, an auctioneer, to sell the captured dinosaurs, and that Dr. Henry Wu has created a new hybrid dinosaur, the Indoraptor, with DNA from the Indominus rex and a Velociraptor. However, the Indoraptor is sociopathic, and the genetic material used to create it is gone. To create a better version of the Indoraptor, Wu needs DNA from the retrieved Indominus rex remains, as well as DNA from Blue, who will also be the mother to the next generation. Maisie warns Benjamin about the auction, and he confronts Mills, who kills Benjamin so the auction can proceed.
Owen and Claire, who had been discovered on the ship, are locked in a cell at the Lockwood estate, while Zia and Franklin manage to evade capture. The auction begins at the estate, and several dinosaurs are sold and shipped. Owen and Claire escape their cell with help from a Stygimoloch. They find Maisie, who shows them the auction and the Indoraptor, which is about to be sold despite Wu’s warning that it is too dangerous. Owen unleashes the Stygimoloch to disrupt the auction. Wheatley subsequently sedates the Indoraptor in its cage and attempts to retrieve one of its teeth as a trophy. However, the animal awakens and kills Wheatley before escaping, after which it kills Eversoll.
Mills locates Owen and Claire, who refuse to let him take Maisie. Mills reveals that Maisie is actually a clone of Lockwood’s deceased daughter, which was the reason Hammond and Lockwood ended their partnership, as Hammond did not believe their cloning research should be used for humans. The Indoraptor arrives, and pursues the humans. Franklin tranquilizes Wu to prevent him from escaping with Blue, who is freed by Zia. The Indoraptor searches for Owen, Claire and Maisie, leading to a battle between Blue and the Indoraptor in Maisie’s bedroom. The Indoraptor is knocked out a window and falls onto a glass roof below. Claire shoots and shatters part of the roof, and Blue knocks the Indoraptor down through the hole, where the creature is impaled by a Triceratops skull on display, killing it.
Blue accidentally hits a propane tank that threatens the lives of the remaining dinosaurs. Maisie sets them free while Mills attempts to escape with a bone from the Indominus rex, but he is killed by the T. rex and a Carnotaurus. Blue escapes into the wilderness, and Owen and Claire take in an orphaned Maisie. Various escaped creatures, including pterosaurs and the Mosasaurus, explore the world, while the auctioned dinosaurs are shipped to their new owners. Malcolm states that humanity must now co-exist with the creatures.