In the colonial era, the main route from Popayán to Bogotá traveled over the Quindío Pass (a.k.a. "La Línea"), passing through the modern-day site of Salento. In 1830 Simón Bolívar traveled the route and ordered that it be upgraded due to its poor condition and strategic importance. However, the town was not established until 5 January 1842, after the Guerra de los Supremos. Political prisoners from that war were sent from Panamá, Antioquia and Cauca to upgrade and maintain the road. After completing their sentences they were given a plot of land in the region.

The site of the penal colony was known as Barcinales, located where Salento is today. However, the main settlement was in the valley in Boquía, where the Boquía stream joins the Quindío river. Families of the prisoners arrived and built their houses in Boquía and established farms upstream in the Cocora valley.

Sometime around 1854 a flood of the Quindío river destroyed the settlement of Boquía, and the survivors rebuilt their houses in Barcinales. They retained the name Boquía for the new settlement, changing the name of the original settlement to Pueblo Viejo.

In 1864 a census of the new Boquía showed that it had 581 inhabitants. The occupational breakdown comprised 148 farmers, 2 carpenters, 1 blacksmith, 11 doctors, 1 lawyer, 2 tailors, 4 laborers, 11 merchants and 11 watchmakers.

In 1865 Boquía was officially declared a municipality and its name was changed again to Villa de Nueva Salento, and the name of Boquía reverted to the original settlement in the valley. The new name of the municipality was given in honor of Salento, a region in the south of Italy.