The long-held paradigm for the evolution of the Patagonian Andes is that the region was low-lying until the middle Miocene, when it underwent substantial surface uplift. However, geologic evidence indicates that the majority of shortening and magmatism in the Patagonian Andes occurred during the Late Cretaceous. I test these competing ideas by reconstructing of the paleoclimate imprint left by the Patagonian Andes, using the strength of the isotopic rain shadow as a way to track the size of the range through the Cenozoic. I use volcanic glasses from three sedimentary sections downwind of the Andes to construct a composite history of precipitation δD from the Paleocene to Miocene. In order to meaningfully interpret the strength of the rain shadow, I estimate the contribution of global climate change to regional precipitation δD and subtract it from the reconstructed water isotope record. This climate change-corrected record is consistent with topography equivalent to modern since the Paleocene, requiring that substantial uplift must have taken place prior to that time, a conclusion that is consistent with existing geologic data. Given the timing of crustal shortening and magmatism, it is likely that surface uplift of the Patagonian Andes largely occurred during the Late Cretaceous.