The church originally belonged to a convent, the Monasterio Real de la Concepción, which was better known as the convent of the Comendadoras de Calatrava. Its origins date back to 1623, when the nuns of the military order of Calatrava moved to Madrid from Almonazid de Zorita, in Guadalajara.

The convent was demolished in 1868, during the Glorious Revolution, only the church remaining standing.  It was built between 1670 and 1678 according to a design by Fray Lorenzo de San Nicolás, although it was completed by Isidro Martínez and Gregorio Garrote. It is in the form of a Latin cross, with a transept and a striking dome, resting on an octagonal tower with eight windows, four of which are open and four sealed. Inside, the magnificent altarpiece created by José Benito de Churriguera between 1720 and 1724, with sculptures by Pablo González Velázquez, is of exceptional interest.

The present day façade is quite different from the original, as during the reign of Isabella II it was completely remodelled by the architect Juan de Madrazo y Kuntz on the orders of the king consort, Francisco de Asís. The change consisted in applying a red terracotta colour to the whole façade and introducing neo-Renaissance decorations, largely inspired by the architecture of Milan, such as the rose window in the central section reproducing the cross of Calatrava.