In which historical region is most of the first Assassin's Creed set?

Most of the first Assassin's Creed is set in the Holy Land.

The historical portion takes place during the Third Crusade in the late twelfth century. Altaïr Ibn-La'Ahad travels among cities including Jerusalem, Acre, and Damascus while carrying out missions connected to the Assassin Brotherhood and the Templar Order.

The phrase “Holy Land” refers broadly to the region containing these important medieval cities. The game uses a fictionalized version of the period rather than presenting a complete documentary reconstruction, but it places its major political and military conflicts against the Crusades.

This setting differs from Assassin's Creed II, which centers on Renaissance Italy, and Assassin's Creed III, which uses the American Revolution as its backdrop. The first game also includes modern-day scenes involving Desmond Miles and the Animus.