When Blaine was still working under Team Rocket, he artificially engineered Mewtwo from the genetic material in Mew's eyelashes together with his own cells. After Mewtwo broke away from the lab, their cellular connection allowed Blaine to track it down, and captured it with Red's help. Mewtwo fought alongside Yellow during the Cerise Island incident, and was later set free when Entei burnt off the connection it shared with Blaine. It returned during the Sevii Island incident, and worked together with Red, Green and Blue to stop Team Rocket's evil scheme on Deoxys. It fought Deoxys on the TR Battle Airship and gained victory marginally. After the Dex Holders were petrified by the clash between its power and Darkrai's, it chased after Sird all the way to Sinnoh. Afterwards, it ended up in Kalos, where it became the protector of the Pokemon Village. It also gained the ability to Mega Evolve after reuniting with Blaine.