"[citation needed] According to the Greek myth, Heracles found curative herbs here to heal his wounds.

The name was changed to Antiochia Ptolemais (Ἀντιόχεια Πτολεμαΐς) shortly after Alexander the Great's conquest, and then simply to Ptolemais, probably by Ptolemy I Soter, after the Wars of the Diadochi led to the partition of the kingdom of Alexander the Great and its inclusion first into the Egypt-based Lagid empire, then in the Seleucid Empire.

It became a colony in southern Roman Phoenicia, called Colonia Claudia Felix Ptolemais Garmanica Stabilis.

In 4 BC, the Roman proconsul Publius Quinctilius Varus assembled his army there to suppress the revolts that broke out in the region following the death of Herod the Great.

In 66, Gessius Florus, the Procurator of Judea, conducted an initial massacre of the Jews living in the city.

The next year, the Roman military commander Vespasian, accompanied by his son Titus, moved from Ptolemais to suppress a Jewish uprising in the Galilee campaign.

After the destruction of Jerusalem many Jews settled in Ptolemais, that was losing its original Phoenician characteristics since Augustus times.

After Hadrianic times, Ptolemais was the commercial center & port of Jewish Galilee and was starting no longer part of Phoenicia.

In 351, Constantius Gallus suppressed a Jewish rebellion and massacred the Jews of Akko-Ptolemais, who were starting to be the majority of the city's population and rejected Roman domination.

[5] The Apostle Paul, returning from his trip to Macedonia and Achea, landed at Tyre, and from there sailed to Ptolemais, where he stayed some days with the local Christian community (Acts 21.7).

Long after the Crusader states had perished, the Catholic church nominally restored the see (linked to the Acre succession) as a titular see, actually twice, in different rite-specific branches.