El Puerto de Santa María is located on the banks of the Guadalete River about 10 km northeast of Cádiz, across the bay of Cádiz.

In 711, Arab from the North of Africa conquered southern Spain. They named the place Alcanatif which means Port of Salt, due to the old salt industry of Phoenicians and Romans. In 1260, Alfonso X of Castile conquered the city from the Moors and renamed it Santa María del Puerto.

This was one of the most importants towns of the Kingdom of Seville throughout the late middle ages. Christopher Columbus's first expedition to the Americas set sail from here. Later El Puerto was the residence of several wealthy merchants who operated Spain's trade with the Americas.

The construction of the Iglesia Mayor Prioral is documented as early as 1486. In 1493 the church was already open for worship, although it would take years to complete. The late Gothic façade probably ruined, like other parts of the church, as a result of the earthquake of 1636, is preserved from this first stage. The effects of this earthquake caused significant damage, with the main nave of the church collapsing. A rebuilding of the church was then undertaken that lasted almost the entire second half of the 17th century. It was partly rebuilt in the Baroque style so the church contains both Gothic and Baroque architecture.