Along-strike geological segmentation in the Andean chain has been recognized at various scales and is usually attributed to changes in plate motion vectors, as well as the upper-plate expression of differing subducted slab age, strength and composition. We present new multi-phase 40Ar/39Ar, apatite fission-track and zircon and apatite (U–Th)/He data from a north–south-oriented traverse between 35 and 388S along the Principal Andean Cordillera of Chile that reveal (1) rapid cooling at 18 and 15 Ma, which can be attributed to both thermal relaxation following magmatic intrusion and regional-scale exhumation, and (2) along-strike differences in the extent of exhumation since 7.5 Ma that may be a consequence of the subduction of the Juan Fernandez Ridge above the flat-slab segment at 328, since 10 Ma. A comparison of the response of the South American Plate to the collision of the Carnegie, Nazca and Juan Fernandez ridges suggests that slab flattening is not the dominant driving force that exhumes the upper plate in these settings. Rather, the extent of exhumation is controlled by pre-existing structural weaknesses, the time duration of the dynamically supported topography, and climate.