The Punta del Cobre district near Copiapo is a center of iron oxide-copper-gold (IOCG) mineralization spatially and temporally associated with regional sodic-calcic hydrothermal alteration, the Atacama fault system (AFS), and two phases of Early Cretaceous magmatism. Here, we investigate the spatiotemporal and geochemical relationships between magmatism, ductile deformation, and hydrothermal alteration along the similar to 200 to 300-m-thick steeply NW-dipping Sierra Chicharra shear zone, interpreted to be the major strand of the AFS. Mylonitic fabrics and oblique sinistral-reverse kinematic indicators together record coaxial flattening in a transpressional regime. Deformation on the AFS took place before, during, and after intrusion of the synkinematic Sierra Chicharra quartz diorite of the Coastal Cordillera arc at similar to 122 Ma and terminated before intrusion of the unstrained similar to 114 Ma Sierra Atacama diorite of the Copiapo batholith. Geochemical data show that the Copiapo batholith was more mafic and more K-rich than the calc-alkaline Coastal Cordillera arc. This time period thus overlaps IOCG mineralization in the Punta del Cobre district (similar to 120 to 110 Ma). Multiple phases of sodic-calcic alteration in and around the AFS shear zone are recognized. Textures of altered rock in the shear zone show both synkinematic assemblages and post-kinematic hydrothermal oligoclase. A similar to 775-m-long andradite vein that cuts the shear zone formed broadly at the end of magmatism in the district (similar to 95 Ma). Oxygen isotope ratios from the vein indicate that hydrothermal fluids were likely magmatically derived. Together, this work shows the AFS-related shear zone and nearby IOCG mineralization developed in a regional transpressional regime produced by SE-directed oblique convergence across a NE-striking shear zone. IOCG-related magmatic-hydrothermal fluids exploited this transcrustal shear zone to produce multiple episodes of regional sodic-calcic alteration formed from fluids exsolved from magmas or driven by the heat of the Coastal Cordillera arc and Copiapo batholith.