Abstract We combine low-temperature thermochronology apatite (U–Th)/He data and semi-analytical modeling of dynamic topography to investigate the role of slab window and climate on cooling/heating history and relief evolution of the Patagonian Cordillera. In particular, we discuss a new thermochronological dataset consisting in 22 samples divided into four elevation transects. Sampling sites were chosen at the same distance from the trench (250–300km), on the leeward eastern side of the orogen, for latitudes ranging between 45°S and 48°S to detect a potential northward migration of the thermal signal associated with the northward migration of the slab window. We show that history of heating and cooling for this region of the southern Andes compares well with the northward migration history of slab window. In particular, a phase of heating is recorded at 15–10Ma to the south and at ≤5Ma to the north, preceding by ∼5Ma the opening of the slab window beneath Patagonia, followed by a phase of rapid cooling and denudation to the south, with values as high as 650m/Myr between 5 and 3Ma. We also show that present-day latitudinal topographic variations require a support by dynamic topography associated with slab window.