The first Assassin's Creed game to feature Desmond Miles as a playable modern-day protagonist is Assassin's Creed.
Desmond is a former Assassin descendant captured by Abstergo Industries, a company secretly controlled by Templars. Through the Animus, he relives the memories of his ancestor Altaïr Ibn-La'Ahad while researchers seek information connected to the Pieces of Eden.
Desmond's modern-day sections are playable, but most of the original game's action takes place in Altaïr's memories during the Third Crusade. This dual structure became one of the defining narrative features of the early series.
Assassin's Creed II continues Desmond's story and introduces Ezio's memories, so it is often remembered as the first title with a substantial modern storyline. However, Desmond first appears as the playable modern-day character in the original 2007 game.