The Pijao inhabited the southern parts of Tolima during pre-Columbian times. The name of the department comes from the Pijao word for "snowed". The Panche, of the same linguistic family as the Pijao, populated the northern regions of Tolima, close to the Magdalena Valley. Renowned as fierce warriors, the Panche were widely known for fighting the Muisca over the control of emerald mining territories. They fought against a Spanish-Muisca coalition and were first defeated in the Battle of Tocarema on August 20, 1538.
Spanish colonization of the region began in 1537 with Sebastián de Belalcázar travelling from the south of later Colombia, where he had founded Cali and Popayán in 1537. He set north to finally reach the area where Gonzalo Jiménez de Quesada had founded Bogotá on August 6, 1538. On its way, De Belalcázar founded the settlement that would become known as Ibagué. De Belalcázar traveled until he reached the settlement of Flandes in Tolima, before heading east towards the Bogotá savanna. Later conquests were executed by captain
Andrés Lopez de Galarza, who founded the city of Ibagué and established the municipality of Cajamarca in the west of the department. These two cities would become an important part of the
Eje Cafetero ("Coffee Axis").