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This church, with a design by the architect Fray Lorenzo de San Nicolás, began construction in 1641 and concluded works 20 years later. Inside is an exquisite Cristo yacente by Gregorio Fernández and for a time also held Cristo crucificado by Velázquez until its transfer to Prado Museum. It was declared a National Monument in 1943.

One of the greatest treasures boasted by San Plácido is the main altarpiece, an Annunciation by Claudio Coello, who also painted a further two altarpieces located on the arms of the transept.  The frescos on the dome, on the vaulted ceiling of the presbytery and the central nave are also of great artistic value. Some of the paintings are attributed to Francisco de Ricci and other Italian painters from the entourage of Diego Velázquez.

Another of the most prominent elements is the Sepulchre chapel, where the famous Christs by Velázquez and Gregorio Hernández once hung, and which was demolished in 1908 on account of its ruinous condition. Located in the district of Malasaña, it was reconstructed in 1912 by the architect Rafael Martínez Zapatero.