A balanced cross-section spanning the Eastern Cordillera and Subandean Zone of southern Peru (13–15°S) constrains ~130 km (38%) of Cenozoic orogen-normal SW–NE Andean deformation accommodated by thick- and thin-skinned retro–arc fold–thrust belt shortening that overprinted pre-Andean Triassic normal faults. Zircon and apatite (U–Th)/He ages demonstrate continuous Oligocene to Miocene cooling of the Permo-Triassic Coasa pluton in the Eastern Cordillera. Zircon (U–Th)/He ages (~34–18 Ma) are reset and define a steep age versus elevation relationship. Apatite (U–Th)/He results reveal reset ages that define two spatially separated groups with ages of ~30–26 Ma and ~17–11 Ma. Detrital zircon U–Pb geochronologic results from Cretaceous–Cenozoic siliciclastic rocks from the Altiplano/Eastern Cordillera record Andean fold–thrust belt and magmatic-arc sediment sources. Correlative Subandean Zone rocks preserve a cratonic sediment contribution, with minor Andean sediment appearing in some Cenozoic rocks. We propose that earliest Andean deformation and structural compartmentalization of the Eastern Cordillera was linked to selective inversion of inherited Permo-Triassic basement-involved normal faults that guided subsequent thick- and thin-skinned deformation. Provenance variations between the hinterland and foreland depocentres reveal competing eastern and western sediment sources, reflecting an axial zone in the Eastern Cordillera that coincided with the inherited Triassic graben and impeded sediment source mixing. Our zircon and apatite (U–Th)/He ages are consistent with published constraints along strike and support pulses of Eocene to late Miocene exhumation that were likely driven by normal fault reactivation and protracted Eastern Cordillera deformation.