The central Andes is the most important copper province on the planet, producing over 40% of the world’s annual output. Giant porphyry copper deposits in the central Andes cluster in discrete geographic camps of a similar age, indicating that exceptional transient geologic processes affected localized regions of the lithosphere around the age of mineralization. The development of favorable regions of lithosphere for significant metal concentration are thought to be linked to the overlap of structural pathways that focus fluid and magma flow from the mantle to upper crust. This research employs a multi-scale and multi-disciplinary approach to understand the nature of the structural architecture thought to control the focused vertical ascent of fluids and magma through the lithosphere. Field mapping undertaken at multiple scales throughout the central Andes demonstrates that on the surface a translithospheric fault is expressed as linear zones of brittle faulting, 10–25 kilometers wide and hundreds of kilometers long. This is interpreted to reflect the upper crustal propagation of the underlying zone of basement weakness through younger sequences in the geologically active convergent plate margin. We postulate that the translithospheric fault architecture of the central Andes formed in response to the interplay of the orientation of accreted terrane suture zones, inherited structural weaknesses and the orientation of Paleozoic and Mesozoic extensional events. During compression and lithospheric thickening, these steep zones of lithospheric permeability were reactivated during periods of high lithospheric coupling, which provided a permeability pathway from the upper mantle to the upper crust, through the lower crust during high strain events. A compelling relationship is observed between the locations of known giant porphyry deposit camps and where two or more translithospheric faults intersect. Such regions are inferred to have been zones of deep dilation, triggered during transient events that affected the stress field