Porygon2 first appeared as a Porygon in A Tale of Ninetales, when Blue bought him from the Rocket Game Corner. After Blue let Porygon out of its Poké Ball, it ran away, causing Blue to run into Red. Because of this the two accidentally trade their Pokémon. During the three days that Red has Blue's team he attempts to get them to relax and open up to him, with little success. They later traded back, while keeping the caring attitude that Red installed in them.
In Striking Golduck, Porygon was Blue's last resort to fight Agatha's Gengar. Because Gengar would hide in the shadows and attack with Counter, Blue decided to use Porygon's Conversion to turn into a Ghost-type. Porygon was then able to counter Gengar's Counter attack but was unable to get Gengar out of the shadows long enough to land a finishing attack. Blue eventually managed to lure Gengar out of the shadows and had Porygon finish it with Psybeam.
In Red and Blue Make Purple Opponents, Porygon2 is used alongside Golduck in a double battle against Red and his Snor and Gyara. Gyara starts the battle off with his AbilityIntimidate, and Blue responds by having Golduck use Iron Tail and Porygon2 use Tri Attack on Red's Pokémon. Red then has Gyara counterattack with Body Slam on Porygon2, while Snor attacks Golduck with Strength. Gyara next uses Hyper Beam on Golduck, and Golduck uses Dig to hide and avoid further damage. Red counters by having Snor use Earthquake, dealing damage to Porygon2, twice the damage to Golduck due to him being underground, which causes him to faint, and Gyara being unaffected due to him being part Flying-type. As Red celebrates he notices that Gyara had been paralyzed by the effects of Tri Attack. Blue takes the opportunity to switch in Porygon2 for Scizor.
In Once More into the Unown, Porygon2 uses its cyber abilities to enter into the Trainer Tower's computer system "R". Using the Salac Berry Blue gave it Porygon2 quickly reaches the central nervous system and attacks with Zap Cannon, disabling it. Not long after this "R" recovers and traps Porygon2 with a virtual lock.
As a Porygon, it was originally disobedient and would run away. However, after Blue and Red's temporary trade, it became more affectionate towards Blue and followed his orders from then on. As it is a man-made Pokémon designed to move around cyberspace, Porygon2 has been in use mainly via Blue's Pokédex as a surprise attack.