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The city was named after a spring, Kyre, which the Greeks consecrated to Apollo and was also the seat of the Cyrenaics, a famous school of philosophy in the 4th century BCE, founded by Aristippus, a disciple of Socrates; it was then nicknamed the "Athens of Africa". Cyrene became part of the Ptolemaic Kingdom controlled from Alexandria during the 3rd century BCE, before becoming Roman territory in 96 BCE when the Ptolemies bequeathed Cyrenaica to Rome.
In 47 BCE, the Medjay Bayek of Siwa pursued the Roman proconsul and Order of the Ancients member Flavius Metellus to Cyrene. Upon arriving in the city, Bayek met with Diocles, a friend of the Greek healer Praxilla whom Bayek had met in a farm south of Cyrene. Diocles directed Bayek to the Roman Akropolis, a fortification wherein Flavius resided. Bayek infiltrated the fort and confronted the Roman, killing him and retrieving the Apple of Eden from him.
- Cyrene is depicted in the game to be much closer to Alexandria than it was in reality. It was actually located almost 500 miles west, near the modern-day village of Shahhat in Libya.
- The mosaic seen in the agora concept art appears to be inspired by the Stag Hunt Mosaic from Pella.
- The Roman soldiers depicted in the various artworks wear anachronistic equipment typical for the mid 1st century AD.