It is the only synagogue in Izmir, which indicates the origin of its founders with its name. It is estimated that this synagogue was founded in 1569 by Jews of Portuguese origin who emigrated from North Africa and Venice.

This synagogue is one of the six synagogues known to have existed during the reign of Rabbi Yosef Eskapa, which corresponds to the years around 1620 and it was known as the biggest synagogue in those times.

Portuguese Synagogue occupied an important place in the events of Sabetay Sevi's return to İzmir in 1665. This synagogue, considered to be the stronghold of the opponents of Sabetay, closed its doors to Sabetay Sevi with the expansion of the Sabetayist movement. Against this move, Sabetay and his followers intruded into the synagogue by breaking the door and they dismissed the rabbis, the leaders of their opponents. Among them was Salomon Algazi, one of the founders of Algazi synagogue. In this raid Sabetay Sevi declared himself as the Messiah of the Jews and proclaimed that day (18 June 1666) as the day of salvation. The Portuguese synagogue then became the center of the Sabetayist movement and most parts of the Jews of Izmir joined the movement. When the people from different parts of the world came to Izmir to join the Sabetayist movement, this growing movement was notified to the palace and when Sabetay was summoned to the palace, the rebellion atmosphere in İzmir calmed down.

The Portuguese synagogue was burned down in 1976 and today it is completely in ruins except its front wall.

The Synagogue is close to Havra Street in Kemeraltı.