In 1550, the administrative building of Misericórdia do Porto on Flores Street was operational and the church, on its southern side, was blessed in 1559 by the bishop of Porto Don Rodrigo Pinheiro. In that same year is indicated as master of the work, Manuel Luís.
The blessing of the church, however, did not imply that it was already completed. Only in 1564 the barrel vault with granite caissons covering the nave was completed and finished continued until 1568.
In the frontispiece, recessed from the front of the administrative building of Misericórdia, the church showed a Corinthian portic.
The chancel, though, was not built. It will only be edified about twenty years later, between 1584 and 1590. The same master Manuel Luís was the designer, with a very similar plan to the chapel of Mosteiro dos Jerónimos church in Lisbon, although on a smaller scale, with a reduced bay and a greater presence of the Flemish ornate of the architect Vredeman de Vries.
In the eighteenth century due to structural problems, largely caused by the high concentration of moisture, a deep intervention in the church was required (1748-54).
It was conducted by the painter-architect Nasoni, who designed the current Baroque façade, and by the engineer Manuel Alves Martins, who produced the plants for the new choir.