Since 1624 the Don Matías territory was occupied by settlers from the city of Santa Fe de Antioquia.

This occupation was the result of new government policies by the crown of Borbón, which the visitor Mon y Velarde applied in Antioquia, seeking the establishment of agricultural colonies in the north of the province.

Those who occupied the present territory of Don Matías were basically mazamorreros, independent miners, who were awarded the title of their plots.

The municipality has had three names: Azuero, San Antonio Infante and Don Matías.

According to figures from the Government of Antioquia based on Quality of Life survey 2004 the prevailing socio-economic strata in the municipality of Don Matías is 2 (low) which includes 70.9% of all homes.