It was built in 1568 by the Malabar Yehudan people or Cochin Jewish community in the Kingdom of Cochin. Paradesi is a word used in several Indian languages, and the literal meaning of the term is “foreigners”, applied to the synagogue because it was historically used by “White Jews”, a mixture of Jews from Cranganore, the Middle East, and European exiles. It is also referred to as the Cochin Jewish Synagogue or the Mattancherry Synagogue.

The synagogue is located in the quarter of Old Cochin known as Jew Town, and is the only one of the seven synagogues in the area still in use. The complex has four buildings. It was built adjacent to the Mattancherry Palace temple on the land gifted to the Malabari Yehuden community by the Raja of Kochi, Rama Varma. The Mattancherry Palace temple and the Mattancherry synagogue share a common wall.
The first synagogue of the Malabari Jews in Cochin was destroyed in the Portuguese persecution of the Malabari Jews and Nasrani people of Kerala in the 16th century. The second synagogue, built under the protection of the Raja of Cochin along with Dutch patronage, is the present synagogue. It is called Paradesi synagogue because it was built with Dutch patronage at a time when Kochi was under Dutch occupation, thus the name paradesi synagogue or “foreign synagogue”.