Like his cousin, Caldas studied in the Seminary of Popayán, where he met others of the leaders of the Colombian independence movement like Francisco Antonio Zea.

Also like his cousin, in 1788 and pressed by his father he moved to Santafé (modern day Bogotá) to study jurisprudence in the Colegio del Rosario, where he obtained a bachelor's degree in 1793.

[2] His studies and records of the time survive in both his letters and memoirs, including a map of the course of the Prado river in the department of Tolima, notes about medicinal trees, a description of the stone hieroglyphs in Aipe and of the statues at San Agustín, experiments to determine whether an insect was venomous, and many others.

[2] After traveling through Peru and Ecuador, and across the New Kingdom of Granada exploring the newfound land, studying flora, fauna, geography, meteorology and cartography, Caldas returned to Santafé in 1805, where he started working for the Botanical Expedition.

[2] In 1809, following the death of Mutis, future independence leaders like Caldas' cousin Camilo Torres, and Antonio Nariño, started meeting clandestinely in one of the halls of the Observatory.

One of his first actions as a president was the formation of the Army Engineer Corps, and Caldas was then appointed to them as a Captain, and charged with making plots of roads and itineraries.

Caldas was part of the troops sent by Nariño, under the command of General Antonio Baraya, to defeat the federalists that were assembled in the Congress of the United Provinces in Tunja.

After being defeated in the rebellion, Caldas, fearing reprisals, escaped to Popayán, but finding that it had been overtaken by the royal troops commanded by future viceroy Juan Sámano, went then to the province of Antioquia.

By the end of 1814, Nariño had been defeated and arrested by the Spanish crown, and Bolívar and his army had forced the submission of Cundinamarca to the United Provinces.

The federalist General Government, which had been established in Santafé, with growing concerns about the possibility of a Spanish reconquest following the start of Morillo's campaign, then called Caldas to appoint him with the creation of a similar Military School, and to build bridges, trenches, and fortifications around the city.

On the way, however, future viceroy Sámano gained a victory over the Republican troops in the Battle of la Cuchilla del Tambo, reconquering Popayán, and Caldas was forced to hide in the Paisbamba Farm in Sotará, where he was soon arrested by the Spanish Royalists.

[2] He was then sent back to Santafé, and executed by a firing squad on October 29, 1816, in the San Francisco Plaza[6] by orders of Morillo, Count of Cartagena.

When Caldas was about to be executed and the people present at the place appealed for the life of the scientist, Morillo responded: "Spain does not need savants" (Spanish: "España no necesita sabios").