It is named after and holds the relics of Saint Isidore, who is patron of Madrid, as well as his wife, Santa María de la Cabeza.

[1] The building replaced the 16th century parish church of Saints Peter and Paul, which had been demolished to make way for the Imperial College as per the will of Maria of Austria, empress consort of Holy Roman Emperor Maximilian II.

Until then, the church also housed the Holy Christ of the Good Death, along with images the Blessed Virgin Mary, and Saint Isidore – works by Juan de Mesa.

In 1936, at the outbreak of the Spanish Civil War, the building caught fire, causing the dome to collapse and destroying many works of art including the Rodríguez high altar, as well as paintings by Luca Giordano Ricci.

After the War, the church was painstakingly restored over two decades, with workers attempting to recreate its original features, such as a faithful replica of the Rodríguez high altar.