In pre-Spanish conquest times, the Guanes lived in the San Gil area. They were related to the Muisca, of the Chibcha linguistic family. The Guanes were still here when the Spaniards arrived, but were quickly exterminated by the conquering forces. Only 351 survived and were relocated to the village of Guanes.

San Gil as we know it today was founded in 1689 by don Gil Cabrera y Dávalos by decree of the Spanish king. The town was originally named for don Gil, and later for the saint of the same moniker.

The sparks of Independence ignited in the villages near this colonial town. In 1781 mestizo José Antonio Golán led the comunero revolt in Charalá; similar uprisings occurred in Mogotes, Onzaga and Socorro. A number of important battles occurred in this region. The Batalla de Pienta of 1819 resulted in heavy losses to the viceregal troops, which helped the rebels later win the Battle of Boyacá.

San Gil and surrounding pueblos were flashpoints of the 20th century civil wars, especially the Guerra de Mil Días at the beginning of the millennium and the disruptions that arose after Liberal presidential candidate Jorge Eliécer Gaitan's assassination in 1948.