Which Pokémon game was the first in the series to offer a female protagonist?

Pokémon Crystal was the first Pokémon game in the series to offer a female protagonist.

Released for the Game Boy Color in Japan in December 2000 and internationally in 2001, Crystal is an enhanced version of Pokémon Gold and Silver. For the first time in a main-series Pokémon game, players could choose to play as a girl rather than using only the default male protagonist.

The female player character is commonly known as Kris. Crystal also added animated Pokémon sprites, extra story material centered on Suicune, the Battle Tower, and other refinements to the second-generation formula.

This feature is sometimes incorrectly attributed to Pokémon Ruby and Sapphire, which introduced the player characters Brendan and May on the Game Boy Advance. Those games expanded the choice with a new generation, but Crystal introduced the option itself. Crystal was also the first Pokémon game incompatible with the original monochrome Game Boy.