Structural, stratigraphic, and geochronologic constraints from the Eastern Cordillera in the central Andean plateau of southern Peru (14-15°S) demonstrate the existence and position of major pre-Andean structures that controlled the accumulation of Triassic synrift fill and guided subsequent Cenozoic deformation. The timing of initial clastic deposition of the Triassic Mitu Group is here constrained to ~. 242-233 Ma on the basis of detrital and volcanic zircon U-Pb geochronology. Regionally distinct provenance variations, as provided by U-Pb age populations from localized synrift accumulations, demonstrate Triassic erosion of multiple diagnostic sources from diverse rift-flank uplifts. Stratigraphic correlations suggest synchronous initiation of extensional basins containing the Mitu Group, in contrast with previous interpretations of southward rift propagation. Triassic motion along the NE-dipping San Anton normal fault accommodated up to 7 km of throw and hanging-wall deposition of a synrift Mitu succession > 2.5 km thick. The contrasting orientation of a non-reactivated Triassic normal fault suggests selective inversion of individual structures in the Eastern Cordillera was dependent on fault dip and strike. Selective preservation of a ~ 4 km thick succession of Carboniferous-Permian strata in the down-dropped San Anton hanging wall, beneath the synrift Mitu Group, suggests large-scale erosional removal in the uplifted footwall. Field and map observations identify additional pre-Andean thrust faults and folds attributed to poorly understood Paleozoic orogenic events preserved in the San Anton hanging wall. Selective thrust reactivation of normal and reverse faults during later compression largely guided Cenozoic deformation in the Eastern Cordillera. The resulting structural compartmentalization and across-strike variations in kinematics and deformation style highlight the influence of inherited Paleozoic structures and Triassic normal faults on the long-term history of convergent margin deformation in the Andes.