Which Pokémon game was the first in the main series incompatible with the original Game Boy?

Pokémon Crystal was the first main-series Pokémon game incompatible with the original Game Boy.

Released for the Game Boy Color, Crystal was an enhanced version of Pokémon Gold and Silver and the final second-generation entry. Its color-only status reflected the Game Boy Color’s hardware capabilities, including animated Pokémon sprites, improved presentation and additional visual effects.

Crystal also introduced several notable series features. Players could choose a female protagonist, encounter added story material involving Suicune and explore the Battle Tower. The Japanese release additionally supported the Mobile Adapter GB, which connected the game to Japan’s Mobile System GB service.

Pokémon Gold and Silver remained playable on both the original Game Boy and Game Boy Color, so they are not the answer despite belonging to the same generation. Pokémon Yellow also supported the original Game Boy. Ruby and Sapphire came later on Game Boy Advance and therefore were not the first game to establish this compatibility distinction.