Which Assassin's Creed game is the final main entry starring Ezio Auditore?

Assassin's Creed Revelations is the final main Assassin's Creed game starring Ezio Auditore.

Released in 2011, Revelations follows an older Ezio in Constantinople, where he searches for Altaïr's lost library keys and becomes involved in the political struggle between the Ottoman Empire and Byzantine Templars. The story also contains playable sections featuring Altaïr.

Revelations completes Ezio's main trilogy, following Assassin's Creed II and Assassin's Creed: Brotherhood. It is therefore the last mainline game in which Ezio serves as the central playable historical protagonist.

Assassin's Creed Embers is a separate animated short film that depicts Ezio later in life, so it is not a mainline video game. Brotherhood comes before Revelations, and Assassin's Creed II begins Ezio's story. The distinction between a main game and other media explains why Revelations is the canonical answer here.