Scientist Dr. Fuji is hired by Giovanni, leader of Team Rocket, to utilize his expertise in cloning in order to create a living weapon based on an eyelash from legendary Pokémon Mew. Soon after the weapon is created, it gains sentience and is named Mewtwo.Several years later, Mewtwo has fully awakened from a long slumber in a laboratory on New Island, and learns of his origin as Mew's clone from Dr. Fuji. Infuriated that Fuji and his colleagues see him as nothing more than an experiment, he unleashes his psychic powers and destroys the laboratory, killing Fuji and the rest of the scientists. Giovanni, witnessing the carnage afar, approaches and convinces Mewtwo to work with him to hone his powers. However, after Mewtwo learns of his purpose to be a weapon for Giovanni's benefit, he escapes back to New Island where he plots his revenge against humanity.After Mewtwo rebuilds the laboratory and establishes a base there, he invites several trainers with hologram messages to battle the world's greatest Pokémon trainer at New Island. Ash, Misty, and Brock receive a message and accept the invitation, but when they arrive at the port city, Old Shore Wharf, Mewtwo creates a storm, causing the boats on the wharf to be closed off for safety. As a result, Ash's group are picked up by Team Rocketdisguised as captains on a Lapras-shaped sailboat. After the storm sinks their vessel in the middle of the ocean, Ash and his friends use their Pokémon instead to reach New Island.Escorted into the island's palace by the woman who appeared on the hologram, Ash and the other trainers who were able to reach the island encounter Mewtwo. The woman is revealed to be a brainwashed Nurse Joy after she is released from Mewtwo's mind control. Mewtwo challenges the trainers using cloned Pokémon. Meanwhile, Team Rocket also reaches New Island and explores its inner sanctum with a Mew innocuously following them. After Mewtwo's clones effortlessly defeat the challengers' Pokémon, he confiscates them and expands his clone army. Ash chases after his captured Pikachu down the cloning lab, where Team Rocket's Meowth is also cloned. Ash destroys the cloning machine, frees the captured Pokémon, and leads them to confront Mewtwo and his clones. Mew then reveals itself and Mewtwo challenges it in order to prove his superiority.All of the Pokémon originals battle their clones save for a defiant Pikachu and Meowth, who makes peace with his own clone after realizing the senselessness of their fighting. Horrified at the pain and anguish felt on both sides of the battle, Ash puts himself in between a psychic blast caused by Mewtwo and Mew's fighting, leading to Ash to become stone. Pikachu tries to revive Ash with its electricity but fails. However, the tears of the Pokémon are able to heal and revive Ash. Moved by Ash's sacrifice, Mewtwo realizes that he should not have to be judged by his origins but rather his choices in life. Departing with Mew and the clones, Mewtwo turns back time to just before the trainers leave Old Shore Wharf, and erases everyone's memories of the event.Back in Old Shore Wharf, the now-restored Nurse Joy has returned to reopen the Pokémon Center to shelter the trainers. The storm outside clears up, Ash spots Mew flying through the clouds and tells his friends of how he saw another legendary Pokémon the day he left Pallet Town. Meanwhile, Team Rocket find themselves stranded on New Island but enjoy their time there.After the credits, a brief scene shows Mewtwo, Mew, and the clones flying towards Mount Quena.