As the highest part of the central Andean fold-thrust belt, the Eastern Cordillera defines an orographic barrier dividing the Altiplano hinterland from the South American foreland. Although the Eastern Cordillera influences the climatic and geomorphic evolution of the central Andes, the interplay among tectonics, climate and erosion remains unclear. We investigate these relationships through analyses of the depositional systems, sediment provenance and 40Ar/39Ar geochronology of the upper Miocene Cangalli Formation exposed in the Tipuani-Mapiri basin (15-16°S) along the boundary of the Eastern Cordillera and Interandean Zone in Bolivia. Results indicate that coarse-grained nonmarine sediments accumulated in a wedge-top basin upon a palaeotopographic surface deeply incised into deformed Palaeozoic rocks. Seven lithofacies and three lithofacies associations reflect deposition by high-energy braided river systems, with stratigraphic relationships revealing significant (∼500m) palaeorelief. Palaeocurrents and compositional provenance data link sediment accumulation to pronounced late Miocene erosion of the deepest levels of the Eastern Cordillera. 40Ar/39Ar ages of interbedded tuffs suggest that sedimentation along the Eastern Cordillera-Interandean Zone boundary was ongoing by 9.2Ma and continued until at least ∼7.4Ma. Limited deformation of subhorizontal basin fill, in comparison with folded and faulted rocks of the unconformably underlying Palaeozoic section, implies that the thrust front had advanced into the Subandean Zone by the 11-9Ma onset of basin filling. Documented rapid exhumation of the Eastern Cordillera from ∼11Ma onward was decoupled from upper-crustal shortening and coeval with sedimentation in the Tipuani-Mapiri basin, suggesting climate change (enhanced precipitation) or lower crustal and mantle processes (stacking of basement thrust sheets or removal of mantle lithosphere) as possible controls on late Cenozoic erosion and wedge-top accumulation. Regardless of the precise trigger, we propose that an abruptly increased supply of wedge-top sediment produced an additional sedimentary load that helped promote late Miocene advance of the central Andean thrust front in the Subandean Zone.