Long before the arrival of Rome, the northeast portion of Alexandria had become home to tens of thousands of Jews who had settled there under the Ptolemies and were vitally involved with the city's trade and its intellectual ferment of ideas. Jewish philosophers like Philo of Alexandria famously interpreted their own religion within the context of Judeo-Christian concepts.

Although Jewish refugees probably fled to Egypt after the Babylonian conquest of Palestine and what later became known as the Diaspora by Nebuchadnezzar, when they were dispersed throughout the known world, we really have no good evidence of such from archaeology in Egypt. It was probably not until the wars of Ptolemy I against the rival successors of Alexander the Great (320–301 BC) that the first scale immigration of peoples calling themselves Jews into Egypt. Invading Palestine four times in those wars, Ptolemy I is said to have "removed from the land of the Jews into Egypt up to one hundred thousand people, from whom he armed about thirty thousand chosen men and settled them through the land in the forts". While Aristeas’ numbers are likely exaggerated, various papyri, inscriptions and ostraca from the third century BC nonetheless testify to the presence of substantial Jewish populations in all parts of Egypt.

In fact, as soon as Alexandria was completed, the Jewish people probably began to inhabit specific destricts in the northeast of the city, known simply as "The Jewish District". They were probably very different than their more conservative counterparts in Jerusalem. Though both worshipped the same god, the Alexandrians seem to have found it difficult to identify him as their god. To them, wisdom was far more important than worship. Hence their religious views tended to be more inclusive and philosophical than in other areas of the Roman Empire.

The Jewish school of Alexandria reached its greatest fame under Philo Judaeus, who lived in there during the early years of Christianity. He came from several generations of wealth and his father enjoyed Roman citizenship. His brother, Alexander, held the high office of alabarch at Alexandria, which meant that he was responsible for collecting taxes owed to Rome. This brother may have in fact been the Alexander mentioned by St. Paul in the Acts of the Apostles. If so, he was unquestionably the foremost Jew of Alexandria and indeed one of the richest men in the ancient world.