Cleopatra appears as a major ally in Assassin's Creed Origins.
The game portrays Cleopatra VII during the political crisis that preceded her restoration to power in Egypt. Bayek of Siwa and Aya become involved with her faction as they oppose the Order of the Ancients, a group connected to the later Templar tradition.
Origins is set in Ptolemaic Egypt, beginning in 49 BCE. Cleopatra's alliance with Julius Caesar is an important part of the narrative, and both historical figures appear in the story. The game uses real events as a framework while inventing missions, dialogue, and personal relationships for its fictional protagonists.
Cleopatra is not the only ancient ruler associated with the series: Assassin's Creed Odyssey includes Leonidas, while Assassin's Creed Valhalla features several rulers of early medieval Britain. Origins was released in 2017 and introduced a more role-playing-focused structure.