The Central Andes between 18°S and 36°S latitude strike north-south for 2000 km along the Chilean subduction margin, cross several climate zones from hyperarid to humid and exhibit mean elevations in excess of 4000 m.a.s.l. Here, we investigate the relationships between tectonics, climate and exhumation by inverting low-temperature thermochronological data compiled from the literature (824 ages from 549 samples) and new data (238 ages from 146 samples) to quantify the exhumation rate history of the Central Andes since 80 Ma. Our inferred exhumation rates west of the drainage divide and between 18 and 32°S did not exceed 0.25 km/Ma. Such low exhumation rates are consistent with low shortening rates and arid conditions in this region. Local pulses of exhumation occurred only during the Eocene as response to active deformation and during the Miocene, probably as response to uplift of the western Andean slope. East of the drainage divide between 18 and 28°S, the observed exhumation pattern reflects the onset and eastward propagation of deformation. Here, exhumation occurred locally since the middle-to-late Eocene in the Eastern Cordillera and the Altiplano-Puna and subsequently affected larger parts of these regions and the north-western Sierra Pampeanas during the Oligocene. In the early Miocene (~20 Ma), the Interandean zone started exhuming and at 12-10 Ma exhumation propagated into the Subandean zone. Enhanced shortening rates and intensified precipitation along the eastern deformation front associated with the onset of the South American Monsoon led to increased exhumation rates in the eastern Interandean and the Subandean zones in the Plio-Pleistocene (0.6 km/Ma). Higher Pleistocene exhumation rates are also observed in the northern Sierra Pampeanas (1.5 km/Ma) that can be related to rock uplift along steep reverse faults coupled with high precipitation. South of 32°S on the western side, exhumation rates in the Principal Cordillera increased from ca. 0.25 km/Ma in the Miocene to rates locally exceeding 2 km/Ma in the Pleistocene. Whereas the tectonic regime in the southern Principal Cordillera remained unchanged since the late Miocene, these higher rates are likely associated with enhanced erosion resulting from intensified Pleistocene precipitation and glacial growth in this region, reinforced by isostatic rock uplift and active tectonics. Our study shows that the onset of exhumation correlates mainly with the initiation of horizontal shortening and crustal thickening, whereas the magnitude of exhumation is largely set by the amount of precipitation and glacial erosion and by the style of deformation, which is controlled by inherited structures and the amount of sediments in the foreland.