The evolution of central Patagonia is associated with episodic shortening and extension that have greatly affected the topography of the Cordillera and intraplate belt. The San Jorge Basin is a site of sediment accumulation in the foreland that is surrounded by igneous and broken foreland relief. The latter originated from episodic deformation and reactivation of inherited structures associated with a period of slab shallowing that allowed the far-field transmission of Andean stresses to the foreland. Thus, due to of its location, the San Jorge Basin provides an exceptional opportunity to study the denudation of both Cordilleran and intraplate topography during the Cenozoic, particularly during the late Eocene–early Miocene interval of mild deformation. In this study, we use a single-grain geochronological approach combining apatite fission tracks and Usingle bondPb dating on apatite, along with maximum deposition ages obtained from Usingle bondPb zircon dating for Neogene foreland basin deposits, to distinguish between two distinctive sediment source regions in central Patagonia during the Cenozoic, despite the persistent volcanic signal. A compilation of previously published cooling ages combined with our new data define: (i) a dominant local source from the northern broken foreland from the late Eocene until the early Miocene; and (ii) a widespread source in the Cordillera during the Miocene based on a very uniform thermochronological signal observed throughout the entire foreland. Therefore, this study provides new insights into the variation of in sediment sourcing in the central Patagonian foreland. This variation is primarily controlled by the decrease of post-orogenic erosional processes during a period of relative tectonic quiescence following the highly active Early Cretaceous–middle Eocene time interval.