Deformation and uplift in the Andes are a result of the subduction of the Nazca plate below South America. The deformation shows variations in structural style and shortening along and across the strike of the orogen, as a result of the dynamics of the subduction system and the features of the upper plate. In this work, we analyse the development of thin-skinned and thick-skinned fold and thrust belts in the Southern Central Andes (30–36°S). The pre-Andean history of the area determined the formation of different basement domains with distinct lithological compositions, as a result of terrane accretions during Palaeozoic time, the development of a widespread Permo-Triassic magmatic province and long-lasting arc activity. Basin development during Palaeozoic and Mesozoic times produced thick sedimentary successions in different parts of the study area. Based on estimations of strength for the different basement and sedimentary rocks, calculated using geophysical estimates of rock physical properties, we propose that the contrast in strength between basement and cover is the main control on structural style (thin- v. thick-skinned) and across-strike localization of shortening in the study area.