The evolution of the Main Cordillera of Central Chile is characterized by the formation and subsequent inversion of an intra-arc volcano-tectonic basin. The world's largest porphyry Cu-Mo deposits were emplaced during basin inversion. Statistically, the area is dominated by NE- and NW-striking faults, oblique to the N-striking inverted basin-margin faults and to the axis of Cenozoic magmatism. This structural pattern is interpreted to reflect the architecture of the pre-Andean basement. Stratigraphic correlations, syn-extensional deposits and kinematic criteria on fault surfaces show several arc-oblique structures were active as normal faults at different stages of basin evolution. The geometry of syntectonic hydrothermal mineral fibers, in turn, demonstrates that most of these structures were reactivated as strike-slip +/- reverse faults during the middle Miocene - early Pliocene. Fault reactivation age is constrained by Ar-40/Ar-39 dating of hydrothermal minerals deposited during fault slip. The abundance and distribution of these minerals indicates fault-controlled hydrothermal fluid flow was widespread during basin inversion. Fault reactivation occurred under a transpressive regime with E- to ENE-directed shortening, and was concentrated around major plutons and hydrothermal centers. At the margins of the former intra-arc basin, deformation was largely accommodated by reverse faulting, whereas in its central part strike-slip faulting was predominant. (C) 2016 Elsevier Ltd. All rights reserved.