Stable isotope paleoaltimetry has been widely used to estimate Cenozoic surface elevation of major orogens. The influence of global climate change on stable isotope paleoaltimetry is uncertain, with proposals that warming could cause either overestimates or underestimates of past surface elevations. In this study we increase atmospheric pCO2 by two and four times in an isotope-tracking atmospheric general circulation model to investigate the effect of global warming on oxygen isotopic compositions of precipitation (δ18Op) over the continents. As in other climate models, the response in the GENESIS version 3 model to global warming is an amplification of upper troposphere temperatures through enhanced infrared absorption and a reduction in the surface to upper-level temperature gradient. Due to the temperature dependence of isotopic fractionation, vapor δ18O (δ18Ov) follows suit, leading to a reduction in the surface to upper troposphere δ18Ov gradient. In regions of subsidence, including the major orogens and deserts, downward mixing of 18O-enriched vapor from the troposphere to the near surface further reduces the lapse rate of δ18Ov. As a consequence of these effects, the isotopic composition of precipitation in high-elevation regions, including the Tibetan Plateau, Rocky Mountains, European Alps, and Andean Plateau, increases by 3‰–6‰ relative to that at low elevations. Neglect of this climate effect on high-elevation δ18Op has likely led to underestimates of the surface elevation of Cenozoic orogens.