The founder of San Luis is widely considered to be Clemente Giraldo, a Presbyterian priest who sought to create a trading outpost between the cities of Granada and the Río Magdalena.

Upon arriving in the region from Granada with several families, Giraldo reached a large stone cliff, named "el Castellón" in Spanish, on August 25, 1876, ow considered the official founding date of the municipality.

The settlers tested the fertility of the soil by planting banana trees, beans, sugar cane, and yuca and, after a successful harvest, returned to Granada to deliver news regarding the new settlement.

The city was frequently targeted by various terrorist and paramilitary organizations, including the FARC, ELN, and Frente IX and was subject to kidnappings, murders, and forced displacements.

[11] Since 2015, the city has seen accelerated construction including a new, ongoing investment named Porvenir II, creating a dam, a hydropower plant, and a lake that is expected to attract even more tourism.