Various references in the writings of Flavius Josephus testify to the existence of a Jewish community on the island, which was a thriving cosmopolitan port as well as a religious centre in antiquity. There is also material evidence in the form of the remains of a building, which dates from the 1st century BCE, and has been identified as a synagogue, based on inscriptural data.

Destroyed in 88 BCE during a war between Rome and one of the Greek rulers of the time, Delos never managed to reclaim its dominant position. The island gradually declined, until it became completely deserted, before the end of the 6th century CE.