The Cordillera Blanca detachment fault in the Peruvian Andes is, to our knowledge, the first active detachment to be documented above a modern flat slab. Crustal detachment has unroofed the ca. 8 Ma Cordillera Blanca batholith, now the backbone of the highest mountain range in Peru. Large-magnitude slip along the fault was thermally enhanced by emplacement of the batholith, the penultimate magmatic event prior to flattening of the Nazca slab. However, extensional models based on arc magmatism and crustal thickening alone do not adequately explain the scale or structural asymmetry of a series of young, deep-seated, west-dipping normal faults across Peru. Here we show that the onset of detachment faulting coincided with subduction of the aseismic Nazca Ridge and consequent flattening of the Nazca slab. We propose that slab buoyancy from ridge subduction triggered extensional collapse of the prethickened continental crust, and that this buoyancy drove footwall uplift that exceeds basin subsidence. The west-dipping asymmetry of late Cenozoic extensional faults in Peru may be controlled by a preexisting crustal anisotropy (older thrusts), and/or formation of Riedel-like shears kinematically linked to the flat Nazca slab.