The Cenozoic stratigraphic infill of hinterland and foreland basins in central Colombia holds the record of basin development during tectonic inversion of rift in the context of subduction orogenesis. A comprehensive review of detrital U–Pb geochronologic and thermochronologic data reveals that activation of interconnected fault systems in the hinterland Magdalena Valley and the Eastern Cordillera occurred coevally since Paleocene time. Longitudinal basins were fed by detritus shed from the Central Cordillera carried along axial drainage systems in open basins in times where slow deformation rates prevailed. Faster deformation since Oligocene resulted in the transient formation of internally drained basins. Differential along-strike exhumation and subsidence patterns in the Eastern Cordillera and the foredeep, respectively, document tectonic acceleration since late Miocene, which we attribute to superimposed collision of the Panama arc leading to oroclinal bending in the Cordillera. Our data documents that the inherited structural grain led to the formation of longitudinal drainage patterns, even in closed basins, which seem to be a general feature of early stages of inversion. We hypothesize that the presence of more humid climatic conditions and faster tectonic rates along the range’s eastern margin favoured the development of internally drained basins, as has also been shown in the Central Andes.