Located in the district known as the Barrio de las Letras, already the site of playhouses in the 16th and 17th centuries – El Corral de la Luz and El Corral del Príncipe, now the Teatro Español –, the Teatro de la Comedia first opened in 1875. In 1915, it was gutted by fire and was rebuilt that same year. One century on, it reopened again following a three-year restoration project. It is currently the home of the Compañía Nacional de Teatro Clásico (CNTC).

Agustín Ortiz de Villajos, an architect from Castila la Mancha, who designed the church of El Buen Suceso, the Teatro de la Princesa (now María Guerrero) and the Teatro Circo Price, was commissioned to build the Teatro de la Comedia, which has premiered some of the great Spanish Golden Age classics as well as plays by authors such as Benavente and Galdós, Dicenta, the Álvarez Quintero brothers, and Moratín.

In this temple to the Madrid stage, the great María Guerrero performed between 1892 and 1905. It has regularly been home to performances by the companies of Santacana, Luisa Esteso, Alberto Closas, Ismael Merlo-Diana Maggi, Mari Carrillo, Adolfo Marsillach-Amparo Soler Leal, Rafael Rivelles and Margarita Xirgu.

With a seating capacity of 672 following its remodelling and reopening in 2015, the Teatro de la Comedia also has a separate room measuring 300 square metres that is used for rehearsals by the CNTC as well as the performance of different shows.