Mewtwo's name originates from that of another Pokémon, Mew, from whom its genes originate. The "two" suffix refers to Mewtwo being a cloned and enhanced Mew. The name Mewtwo refers to the species as a whole, as well as to individual specimens in the games, anime, manga, trading cards, and other media, but canonically, there is only one Mewtwo in the Pokémon World.

Mewtwo's body is light purple and has an alien-like appearance, also resembling Mew's to some degree.

Due to its genetic background, Mewtwo’s powers are superior to all other Pokémon, even many of legendary or god-like regard. Mewtwo can employ telekinesis to lift people and Pokémon off the ground, or to perform self-levitation, which allows it to achieve genuine flight. All this can be done with only a minor or nearly no strain on its mind. Mewtwo has the ability to project its thoughts telepathically to others, making it one of the very few Pokémon who can directly communicate with any sort of creature. When in battle with another Pokémon, Mewtwo can easily summon a barrier of telekinetic power to protect its body, as well as erase memories.

Mewtwo in the Cerulean Cave in FireRed/LeafGreen

Mewtwo can be captured in the Fire Red and LeafGreen versions as well. It lives in the Cerulean Cave at level 70. Once caught, Mewtwo can be traded to the other versions. Mewtwo have high Special Attack after Deoxys in his attack form rating and a high Speed and Attack. However its Defense and Special Defense are slightly above average.^[6]

In Pokémon Stadium, Mewtwo is the boss-character of every Round of the stadium; after completing the Gym Leader Castle, the four levels of the Poke Cup, Prime Cup, Pika Cup and Petit Cup, a Level 100 Mewtwo awaits battle, and the player must be able to defeat it with a team of any six or less Pokémon to complete that round.^[7] Pokémon Stadium 2 has these battles much like the previous game, but this time the battle is with the Rival who has three Pokémon at level 50: Lugia and Ho-Oh in addition to Mewtwo.^[8]

In the Nintendo 64 game Pokémon Snap, while Mewtwo is not physically present, an array of glowing crystals is located in the Cave course. If the center crystal is properly snapped, the photograph displays a large, holographic image of Mewtwo, one of the six "signs" required to get to Rainbow Cloud, the final course in the game. Mewtwo also appears in Pokémon Mystery Dungeon as a boss character at the end of the game and is later recruitable in the brutal 99 floor dungeon Western Cave Dungeon.^[9] Mewtwo also plays a cameo in Pokémon Puzzle League.^[10]

Mewtwo as seen in Super Smash Bros. Melee

Mewtwo made its first Smash Bros. appearance in Super Smash Bros. Melee. It is one of four playable Pokémon characters, and has Shadow Ball, Teleport, Confusion, and Disable as its special moves. Although it has a slow running speed, has a light weight and is easy to knock out of the arena, it has quick, strong attack moves and can lift and throw items (and other players) easily. Mewtwo is notable for its unique movements and item use (rather than running or walking, it floats on its feet, and it uses its psychic powers to hold items and enemies rather than its hands). It is currently unknown if Mewtwo will be playable in the game's sequel, Super Smash Bros Brawl.

In the anime Episode 13, "Mystery at the Lighthouse" when Ash, Brock, and Misty arrived at a lighthouse and knock on the door, an image of Mewtwo is seen carved on its door, among other legendary Pokémon.^[11]

Mewtwo also appears in the main anime storyline three times wearing its armor and helmet but its identity is not revealed. Its first appearance is in a Pokémon battle at the Viridian City Gym between Giovanni and Gary, who is defeated quickly.^[12] The second appearance is during a brief scene with Giovanni talking to it.^[13] The final appearance is when Mewtwo destroys and flees from the Gym during episode "Showdown at the Poké Corral".^[14]

However, Giovanni's interfering with the fragile nature of the area results in chaos involving a swarm of disturbed Bug Pokémon, and Ash and his friends, who just so happen to have been in the area when the operation took place, find Mewtwo incarcerated. Because Ash and his friends have no recollection whatsoever about Mewtwo, their instinct is to free him. Though they and Mewtwo are successful in destroying its energy prison, Mewtwo’s life force is in jeopardy, but Ash and his Pokémon carry Mewtwo to Mt. Quena’s healing spring and hurl it into the water, and Mewtwo’s body and soul are restored. Mewtwo comes to another epiphany: That if this natural healing water has a healing effect on his artificial body, then being a clone does not mean that one is automatically “impure”. Rejuvenated, Mewtwo emerges before Giovanni and declares that neither it nor the region belong to the Team Rocket leader. Using all its power, Mewtwo psychically moves the lake and the spring beneath the surface of Mt. Quena, and Giovanni and all of his henchmen, except Jessie and James, are moved away from the mountain with their memories erased. Mewtwo sees that Ash, his friends, Jessie, James and also their Pokémon are virtuous and trustworthy enough not to reveal the mountain’s secrets, so it does not erase their memories again. After thanking Ash for all his help, Mewtwo disbands his army of clones to live as regular Pokémon, and he flies into eternal, yet secluded, freedom.

Mewtwo destroying the lab on Mile Island after its creation.

In Pokémon: The First Movie, Mewtwo stirs from its slumber in stasis a while after its memory is erased and it has matured. When it is told that it is a laboratory specimen for the humans who created it and that they dont care for it, Mewtwo is enraged and destroys the laboratory. It is soon found by Giovanni, who had originally ordered Mewtwo's creation, and succeeds in tricking the Pokémon by telling it that he will help "add value" to Mewtwo's life and make him stronger. Giovanni trains Mewtwo through use of a sort of armor plating in his gym in Viridian City. Upon finding out that Giovanni is using it as nothing more than a tool, it is convinced that humans are immoral. Mewtwo destroys the machinery connected to it and flies away, escaping Giovanni's clutches. It goes to New Island and sets a new goal: a global purge of humans and Pokémon, both of which it believes to be corrupt and weak; the humans in doing whatever they want and their pokémon mindlessly obeying them. Mewtwo's plans are to clone every species of Pokémon to create superior creatures- super clones like itself and wipe the planet clean of all humans and "inferior" Pokémon.

Mewtwo sets in motion its plan to acquire Pokémon for cloning. In order to do this, it sends letters to many trainers including Ash, inviting them to the island to meet "the world's greatest" Pokémon Master. Creating a storm so getting to the island would be more difficult, Mewtwo tests to see who are the worthiest trainers and upon their arrival, it appears before them proclaiming itself to be the world's greatest Pokémon and Pokémon Master. Mewtwo detains the trainers' Pokémon using Thief Balls, a variation of the Pokéball that captures all tamed Pokémon, even those inside their Pokéballs. Mewtwo clones each of them for itself in the lab it created. Ironicaly, he intends to use them like geovani used him. However, a wild Mew that witnessed the scientists with the fossil appears,^[15] and Mewtwo immediately sets the stage for a tremendous battle with it. With that, the ultimate Pokémon battle ensues, and the chaos eventually ends when Ash throws himself into Mewtwo and Mew’s crossfire of Psychic attacks, rendering his body lifeless and stone-like. This shocks Mewtwo, and as all the Pokémon grieve, their tears caress Ash’s body and miraculously revive him. Mewtwo realizes that all living beings have virtue. Then, it erases the memories of all trainers and their Pokémon and teleports them to the places where they received their invitations before taking the Pokémon it cloned along with it on a journey westward, in search of a haven.

Mewtwo stands on a rooftop overlooking a city, cloaked in a brown cape.

The last shot of Mewtwo Returns, the "Adding to Pokémon Lore" segment that preludes the sixth Pokémon movie Pokémon: Jirachi Wishmaker, and the opening sequence to the eighth season of the English anime dub all contain brief scenes where Mewtwo is seen residing amongst the rooftops and alleyways of what is merely described as a faraway city. In the latter two instances Mewtwo is seen wearing a brown cape.

Mewtwo's likeness, however, most recently appeared in the 10th anniversary television special, The Mastermind of Mirage Pokémon. The Mewtwo that appears is a Mirage Pokémon created by Dr. Yung and his "Mirage Battle System". Dr. Yung, under the alias "Mirage Master", creates Mirage Mewtwo to be completely without weaknesses and capable of using any known Pokémon attack, and he plotted to use the entity to get revenge on those who doubted him. It is thought that Dr. Yung stole the information about Mewtwo from some sort of classified Pokémon files accessible with the password Oak gave him or used Pikachu's memory about Mewtwo. Ash and his friends, along with Professor Oak, are there to witness Mirage Mewtwo’s creation and were close to being destroyed by it if it were not for the interference of a Mirage Mew, another Mirage Pokémon created by Dr. Yung that somehow acquired enough sentience to rebel against the Mirage Battle System. Mirage Mew and Pikachu destroy Mirage Mewtwo with everyone’s help and the entire location is destroyed in a flaming wreck; Dr. Yung disappears amongst the flames of his collapsing factory. However, despite marching into a burning laboratory, his remains were not recovered, implying it is possible he is still alive and in hiding.

Mewtwo also appears in the live action musical Pokemon Live, along with Giovanni's mechanical clone, MechaMew2. Mewtwo appears near the end and turns MechaMew2 against Giovanni by using the memories of Ash Ketchum and how MechaMew2 was never shown kindness.

In the anime and all games with spoken dialogue, Mewtwo is voiced by Japanese actor/singer Masachika Ichimura. In the English dub of the first movie, it is voiced by Phillip Bartlett. In the dub of the special Mewtwo Returns, Mewtwo was voiced by Dan Green.