It was first introduced in the video games Pokémon Red and Blue, and later appeared in subsequent sequels and spin-off titles, such as Pokkén Tournament and Detective Pikachu.

A third Mewtwo also appears in the 2019 live-action animated film Detective Pikachu, voiced simultaneously by Rina Hoshino and Kotaro Watanabe.

[9] In these games and their sequels, the player assumes the role of a Trainer whose goal is to capture and use the creatures' special abilities to combat other Pokémon.

[14] According to Pokémon Company president Tsunekazu Ishihara, Mewtwo was expected to be popular with North American audiences, citing their preference for strong, powerful characters.

Kubo Masakazu, executive producer of Mewtwo Strikes Back, explained that they "intentionally avoid using the term 'kuron' [clone]… because the word has a frightening feel".

The notes say that a scientist[1] discovered a new Pokémon in a Guyana jungle, that they named it Mew, and that it later gave birth to a creature they called Mewtwo; the game's Pokédex entry states that Mewtwo was "created by a scientist after years of horrific gene splicing and DNA engineering experiments".

The player is later given an opportunity to capture Mewtwo in the Cerulean Cave, which is accessible only after defeating the game's final bosses, the Elite Four and Blue;[25] in the remakes Pokémon FireRed and LeafGreen this prerequisite was expanded, requiring the player to explore more thoroughly and record information on sixty Pokémon species before access to the cave would be granted.

The character was also the focus of a promotion and downloadable content giveaway for Pokémon Black and White, debuting with its signature move "Psystrike" that can also be learned by leveling up.

[38][39] In Pokémon Puzzle League, Mewtwo, voiced by Philip Bartlett, serves not only as the final opponent, but also as the main antagonist responsible for the game's events.

[42] Mewtwo made its debut in the series in Super Smash Bros. Melee voiced by Masachika Ichimura who reprises his role in Pokémon: The First Movie.

Unlike in the games, it is shown to be the creation of the criminal organization Team Rocket, and is referred to as a clone instead of a genetically modified mammal.

[citation needed] Mewtwo, upon acknowledging the selflessness of Ash's sacrifice, comes to the conclusion that one's actions determine who they are and not the circumstances of their birth.

To save the traumatized Mewtwo, Fuji erases its memories and puts it under sedation until its body finishes developing, leading to the events of the film.

Assisted by Ash and his companions, Mewtwo comes to terms with its existence and defeats Giovanni, removing any memory of itself from him and his soldiers' minds while leaving the others unaffected.

Compared to the original Mewtwo, this one is also conflicted about its existence, yet is more empathic to the point of not being belligerent toward humans, as shown when it protects Ash, Iris, Cilan, and Eric from the rampaging Genesect army.

After defeating Ash and Goh in a battle, Mewtwo decides to leave Cero Island with the rescued Pokémon and teleports them back to the Cerise Laboratory, allowing them to retain their memories of the encounter.

: Pokémon Tales Movie Special, which featured children taking on traits of the characters from the film, including Mewtwo.

[72] In the manga series Pokémon Adventures, Team Rocket created Mewtwo, but some of its DNA is placed inside the Gym leader Blaine.

It eventually helps the main character of the series, Red, fight against Team Rocket leader Giovanni and his Deoxys.

[74] In 1998, Toshihiro Ono was asked to write a story detailing Mewtwo's origin to coincide with the release of Pokémon: The First Movie.

[75] The 52-page comic, presented in the form of a flashback,[76] was replaced midway by "The Birth of Mewtwo" animated short, resulting in little connection between Ono's work and the film.

In it, Mewtwo's creator, Dr. Fuji takes on the role of a coach for the fully developed Pokémon, while his employers, Team Rocket, test its abilities.

[76] Mewtwo's image is utilized for merchandise related to the Pokémon franchise, which includes toys, children's toothbrushes,[77] and a playing piece for a Pokémon-themed version of Monopoly.

[81] Mewtwo also appears on the port side of All Nippon Airways's Pocket Monsters Boeing 747 jumbo jet, alongside Mew.

"[91] Gavin Jasper of Den of Geek compared Mewtwo to Street Fighter series character Akuma, and praised it for having a backstory, personality and motivation unlike many pokémon in the franchise, stating " Genetic engineering in a world of wacky creatures is just asking for trouble and Mewtwo is the payoff.

"[92] Dale Bishir of IGN described him as an icon, and the "go-to 'villain' Pokemon", noting its frequent presence in media for the series, including its starring role in two of the feature films.

: 100 Must-See Japanese Animation Masterpieces as the best villain of the Pokémon film series, and one of Mewtwo Strikes Back's strongest elements.

[95][96] Theology Secretary for the Church of England Anne Richards described Mewtwo as representing a "parable about the pointlessness of force", and praised the character for displaying the Christian value of redemption.

[99] However, Animerica praised Mewtwo as a character with "philosophical depth" as well as for serving as "an adversary of almost infinite power and genuine malice" that the anime series had been lacking.

[103] The book Gaming Cultures and Place in Asia-Pacific compares Sugimori's design of Mewtwo to that of Japanese tokusatsu films, namely monster films like the 1954 Godzilla in creating "monstrous yet familiar silhouettes from the past renewed agency in the form of eyes and expressions which cut through the viewer".