In this research, we compared thermochronological and traditional one-dimensional thermal models across the Middle Magdalena Valley (MMV), Eastern Cordillera, and Eastern Llanos Basins in Colombia. These models allow us to relate cooling/heating histories to exhumation events, subsidence, fault activities, and fluid flow. The Eastern Cordillera and Eastern Llanos Basins are discriminated as prospective zones for hydrocarbon (HC) generation. The De Armas Syncline at the MMV basin shows high thermal maturity (127°C), describing rocks completely depleted in terms of HC generation. The eastern zone of this syncline is buried until it reaches temperatures above 150°C. The contrast between thermal models in the Eastern Cordillera basin suggests a possible sediment supply scenario from the west to the east of the Soapaga Fault. In the Eastern Llanos basin, the thermal histories between both models explain the latest uplift and sediment supply processes from the hinterland zone of the Eastern Cordillera to the foothill zone of the Eastern Llanos basin. In terms of thermal evolution, the three basins are different, reaching different levels of burial and HC maturity. However, in terms of cooling events related to exhumation, the basins have similarities as they are controlled by the mountain building of the Eastern Cordillera of Colombia.