Which city is Assassin's Creed II's opening Renaissance setting?

Florence is Assassin's Creed II's opening Renaissance setting.

The game begins in Florence in 1476 and introduces Ezio Auditore da Firenze, a young nobleman whose life changes after his family is targeted. Florence serves as the first major city in Ezio's story before the game expands to other locations in Italy.

Assassin's Creed II uses several historically recognizable Italian settings. Players later visit Monteriggioni, San Gimignano, Forlì, Venice, and the Vatican area of Rome during the broader campaign. This variety is one reason the game is often remembered as a tour through Renaissance Italy.

Venice is a major location in Assassin's Creed II, but it is not the opening city. Rome is especially important in Assassin's Creed: Brotherhood, while Milan appears in the wider historical background but is not the answer to this question.