Which Assassin's Creed game was the first to feature the city of Rome as its main setting?

Assassin's Creed: Brotherhood was the first Assassin's Creed game to feature Rome as its main setting.

Released in 2010, Brotherhood continues Ezio Auditore's story after Assassin's Creed II. Much of the game is set in Renaissance Rome, where Ezio works to weaken the Borgia family's power and rebuild the Assassin Brotherhood.

Rome functions as a large, connected open-world city rather than a collection of separate primary locations. Ezio can restore shops, landmarks, and services, making the city itself part of the game's progression system. The title also expands recruitment and management of Assassin apprentices.

Assassin's Creed II includes Rome briefly, but it is not the game's main setting. Assassin's Creed Revelations later moves Ezio to Constantinople, while Origins uses ancient Egypt and does not center on Renaissance Rome.