Blue's first appearance was in Pallet Town, where he met up with Red on his way to receive a Pokémon from Professor Oak. When he got to Professor Oak's Lab, Blue was given a Pokédex and chose a Squirtle, as it had a type-advantage over Red's Charmander. Later he again met up with Red again near Viridian City and challenged him to a battle. During the battle Blue's Squirtle easily dodged all of Charmander's attacks and dealt heavy damage ending up in a victory for Blue. In File 2 - Cubone, Blue decided to investigate the Pokemon Tower to get rid of Team Rocket and be a hero. However, once he got there, Blue encountered the ghost of Cubone's mother and ran away. Then he bumped into Red and said that they needed to get out of the Pokemon Tower. Red decided to stay and fight, so Blue continued upstairs, where he found and defeated a Team Rocket Grunt by using his Wartortle. In File 3 - Giovanni Blue helped Red rescue the Silph Co. secretary from Team Rocket. In File 4 - Charizard Blue had officially become the Champion. After defeating the Elite Four, Red faced Blue as his final challenge. Both battled hard but Red eventually won. Later Red found Blue at Professor Oak's house with heavy injuries from battling a Pokemon in Cerulean Cave.
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In File 4 - Charizard, Blue mentioned that he had caught 148 Pokémon of different species.
Unlike in the game, Blue helps Red a few times like in the Pokémon Tower in Lavender town and Silph Co. in Saffron City. He and Red don't battle much, unlike the games. They only fight on Route One and the Pokémon League.