Construction of the church began at the behest of Brother Alonso de Jesús Ortega in 1737 and finalised in 1759.

It was financed by the Hospitaller Order to house the remains of its founder, Saint John of God, born in Montemor-o-Novo, Portugal, although he came to live in Spain at a young age. It boasts a beautiful Baroque façade flanked by towers featuring slate capitals.

It is one of the most important Baroque temples in Spain. It is divided into two sections and features a Latin cross floor plan, a nave with side chapels, two on either side, a main chapel and a choir. The high dome at the transept is particularly noteworthy.

The church chapel houses a solid silver urn that contains the relics of Saint John of God. Its interior is richly adorned with sculptures and images. The fresco paintings depict saints, angels, virtues and episodes from the life of Saint John of God.