Philip III founded this Church at the beginning of the 17th Century. It is a unique church in Madrid due to its ellipsoidal layout, and for having been painted entirely al fresco.

At the beginning of the 17th century, Philip III offered the Church and the adjacent Hospital to Portuguese pilgrims and patients who were passing through Madrid, so it was originally named San Antonio de los Portugueses. In 1640, when the Spanish crown lost Portugal, the temple ceased hosting citizens of Portugal and it remained empty until 1689, when Mariana de Austria gave it to the Catholics of Germany who were accompanying Carlos II’s wife in Madrid. Consequently, it was known as San Antonio de los Alemanes (Saint Anthony of the Germans).

Dedicated since its origins to San Antonio de Padua, the existing building was started in 1624 and several masters of that time participated in its construction, such as Pedro Sánchez, Francisco Seseña and Juan Gómez de Mora. Its interior decoration was completed in several stages and a group of noteworthy painters participated in it, such as Francisco Ricci, in charge of the architectural composition decorating the dome (an example of trompe l’oeil), Francisco Carreño de Miranda, who painted San Antonio’s ascent to the Virgin, or Lucas Jordán, in charge of repainting the fresco columns.