Assassin's Creed Origins primarily begins in 49 BC during Cleopatra's reign.
The game follows Bayek of Siwa and Aya during a period of civil conflict in Ptolemaic Egypt. Its main narrative begins when Cleopatra is fighting for power against her brother Ptolemy XIII, while Julius Caesar becomes involved in the Egyptian political struggle. The story eventually moves through later events, so 49 BC identifies the principal starting year rather than every scene's date.
Origins depicts the formation of the Hidden Ones, the organization that later becomes the Assassin Brotherhood. Bayek and Aya's campaign against the Order of the Ancients supplies the fictional foundation for that origin story, while the game incorporates historical figures such as Cleopatra, Caesar, and Ptolemy XIII.
This date is often confused with 44 BC, the year Julius Caesar was assassinated, or 31 BC, the year of the Battle of Actium. Origins is set earlier, during the final decades of the Ptolemaic Kingdom and before Cleopatra's death in 30 BC.