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The Puna Plateau, adjacent Eastern Cordillera and the Sierras Pampeanas of the central Andes are largely characterized by thick-skinned, basement-involved deformation. The Puna Plateau hosts similar to N-S trending bedrock ranges bounded by deep-seated reverse faults and sedimentary basins. We contribute to the understanding of thick-skinned dynamics in the Puna Plateau by constraining regional kinematics of the poorly understood southern Puna Plateau through a multidisciplinary approach. On the southeastern plateau, sandstone modal composition and detrital zircon U-Pb and apatite fission-track data from Cenozoic strata indicate basin accumulation during the late Eocene to early Oligocene (similar to 38-28 Ma). Provenance analysis reveals the existence of a regional-scale basin covering the southern Puna Plateau during late Eocene to early Oligocene time (similar to 38-28 Ma) that was sourced from both the western plateau and the eastern plateau margin and had a depocenter located to the west. Petrographic and detrital zircon U-Pb data reveal erosion of proximal western and eastern sources after 12 Ma, in mid-late Miocene time. This indicates that the regional basin was compartmentalized into small-scale depocenters by the growth of basement-cored ranges continuing into the late Miocene (similar to 12-8 Ma). We suggest that the Cenozoic history of the southern Puna Plateau records the formation of a regional basin that was possibly driven by lithospheric flexure during the late Eocene to early Oligocene, before the growth of distributed basement-cored ranges starting as early as the late Oligocene. (C) 2015 Elsevier B.V. All rights reserved.