Mewtwo, an immensely powerful Psychic type Pokémon, debuted in Pooh's Adventures of Pokémon: The First Movie. He was created by scientists at a laboratory on New Island. Mewtwo destroyed the lab because he thought the scientists were using him as a mere experiment. Later, Giovanni trained Mewtwo to control his psychic powers, but after he learned why Giovanni was training him to serve him, Mewtwo destroyed his lab. Mewtwo vowed to destroy Earth for betraying him,and rebuilt New Island. Later, Pooh and the others traveled to New Island for a big Pokémon showdown created by Mewtwo. After making Pokémon clones, there was a big showdown between clones and originals. Ash Ketchum stopped the showdown by standing in the middle of the stadium between Mew and Mewtwo's beams of psychic energy. Then, Mewtwo learned that Ash was a person who valued all Pokémon born or created. Mewtwo and the Clones left to find a place where they could live in harmony and peace and used his psychic power to return Pooh and friends home and wipe out the memory of the fight on the trainers.
Later, in Pooh's Adventures of Pokémon: Mewtwo Returns, Mewtwo took Christopher Robin, to be safe from Giovanni. Then, Pooh and his friends reunited w/ Ash, Misty, Brock, and Pikachu to find him at Purity Canyon. Team Rocket's combat unit arrived to take Mewtwo and his clones, and claim Mt. Quena as a new laboratory. Pooh and his pals freed Mewtwo from Giovanni's machines and revived him in the spring water. After that Mewtwo erased Giovanni's memory, spared the memories of Pooh and his friends, returned Christopher Robin to them, and decided to live with them but at Skull. Thus, Mewtwo became the father figure to Pooh and his pals, protective, but calm and level-headed. By the end of Winnie the Pooh And The Secret of Kells he became Aisling's adopted father.
- Mewtwo will encounter Littlefoot, SpongeBob, and their friends in Littlefoot's Adventures of Pokémon: The First Movie and Littlefoot's Adventures of Pokémon: Mewtwo Returns.
- Mewtwo made his first guest appearence in a non-BowserMovies1989 project in Pooh's Adventures of All Dogs Go to Heaven 2 and will guest star again in Pooh's Adventures of Star Wars: The Clone Wars, and Pooh's Adventures of Fievel's American Tails.
- Mewtwo is also good friends with Princess Celestia, Princess Luna and Shifu.
- Just like Charizard, Mewtwo can mega evolve into two different forms. When it mega evolves into Mega Mewtwo X, its type changes into a Psychic/Fighting-type. However, it keeps its original type when it is a Mega Mewtwo Y.
- In Genesect: The Legend Awakened. Mewtwo is a female.
- Mewtwo will meet Hubie, Marina and their friends in Hubie and Marina's Adventures Of Pokemon The First Movie and again in Hubie and Marina's Adventures Of Pokemon: Mewtwo Returns.