Real de Catorce ('Royal Fourteen') is named for 14 Spanish soldiers killed here in an ambush by Chichimeca warriors. Other sources tell that in the beginning the name was "Real de Álamos de la Purísima Concepción de los Catorce" (Real de Alamos of the Immaculate Conception of the Fourteen). Although a town had been there for many years, silver was discovered in the local mountains in 1772 and a few years later in 1779 the village was officially founded. The parish church was built between 1790 and 1817. Real de Catorce's heyday was in the late 19th century, when it had a population of 15,000, with some of Mexico's richest silver mines and a mint, as well as a bullring and shops selling European luxury goods. It was almost completely abandoned when the price of silver plummeted after 1900; only a few people remained in this ghost town, eking out a living from mine tailings and an annual influx of pilgrims to a reputedly miraculous image of St. Francis in the parish church. Today, its main income comes from tourism.

Several major commercial motion pictures have been filmed in Real including Bandidas (featuring Salma Hayek and Penélope Cruz), The Mexican (featuring Brad Pitt and Julia Roberts), and some scenes of The Treasure of the Sierra Madre (featuring Humphrey Bogart), and of Puerto Escondido, directed by Gabriele Salvatores.