Located in the centre of the Argentinean Patagonia between 46° and 49°S, the Deseado Region represents the foreland domain of the Southern Patagonian Andes. Its geology is characterized by thick Mesozoic sequences which, at its eastern sector, present a Mesozoic and Cenozoic geologic evolution which has been strongly determined by the development of three major tectonic phases. The present research is based on field geological mapping, interpretation of seismic and aeromagnetic data, as well as satellite image analysis. This approach has allowed us to identify and characterize the deformation that occurred throughout Jurassic, Cretaceous and Miocene times. We interpret that the most relevant structural features are the result of normal faulting generated as a response to the Jurassic rifting stage. These extensional features have strongly influenced the subsequent geometry and distribution of younger Cretaceous and Cenozoic structures. The Jurassic extensional deformation, which affected major areas of Southern Gondwana, is the product of a major intra-continental rifting stage which was accompanied by synkinematic volcanism. This tectonic regime is characterized by SW-NE directed extension that generated major oblique WNW trending faults accommodating regional dextral-extension. In the study area, this tectonic regime is inferred from the geometries of major fault systems interpreted from available seismic reflection data, as well as from the spatial distribution and orientation of the extensional fracturing associated with the opening of hybrid and dilatational siliceous epithermal Au–Ag veins. Following the Jurassic rifting stage, a more restricted Cretaceous -post-Neocomian-compressional tectonic phase took place. Throughout this period, we interpret the previously formed Jurassic extensional structures to have been reactivated under sinistral transpression. Deformation during this period generated sinistral-reverse WNW belts of deformation, which accommodated reverse faulting, imbricate thrusts, dextral and sinistral R1 and R2 shears and disharmonic folds due to a buttress effect. Under the post-Oligocene Andean regime, W–E directed compression acted on previously-formed N to NNE-oriented normal faults. Compression and shortening uplifted a series of narrow and sub-meridional ranges which run as a 200 km long inversion-related tectonic front along the Patagonian foreland. Between 47°11′ and 48°40′S, one of these NNE ranges divides the entire Deseado Region into two distinctive structural domains. Whilst the western domain presents dominant NNW morphotectonic features, that to the east appears highly dominated by WNW fabrics of Jurassic and Cretaceous age. The structural features of the Eastern domain appear to extend further north of the Deseado Region towards the vicinity of the San Jorge Gulf. This WNW-trending belt hosts pre-Upper Cretaceous rocks and pre-drift basement rocks which include igneous Paleozoic metamorphic rocks and Permian to Triassic sedimentary units. The Deseado region’s epithermal Au–Ag Jurassic vein systems result from the infilling and deposition of low temperature hydrothermal fluids within dilatational and hybrid structures. These spectacular vein systems are compatible with the regional SW-NE extension direction controlled by the Jurassic intra-continental rifting of southern Gondwana. Dilatational and hybrid veins are preferentially hosted by fractures in the Jurassic volcanic rocks, while the veins located within the pre-volcanic basement preferentially infill normal faults. Finally, most of these epithermal vein fields where exhumed during a moderate phase of inversion during Cretaceous times.