In Assassin's Creed Brotherhood, Rome is controlled by the Borgia family at the start of the story.
The game follows Ezio Auditore as he works to weaken Borgia power in Rome. Cesare Borgia commands the family's military ambitions, while Rodrigo Borgia, known in the game as Pope Alexander VI, represents its political authority.
Rome functions as Brotherhood's principal open-world setting. Ezio liberates districts by defeating Borgia influence, completing missions, and rebuilding shops and landmarks. This structure connects the city itself to the game's progression system.
Florence and Venice are strongly associated with Assassin's Creed II, while Constantinople is the main setting of Assassin's Creed Revelations. Rome is the city whose occupation drives Brotherhood's central conflict.