Climate reconstructions based on stable isotopes in tree rings rely on the assumption that fractionation-controlling processes are strongly linked to meteorological variables. In this context, we investigated the climate sensitivity of 350 years of carbon and oxygen isotope ratios of tree ring cellulose from European larch obtained at a high-elevation site in the Swiss Alps (∼2100 m above sea level). Unlike tree ring width and maximum latewood density, which contain only summer temperature information at this site, we found that our stable isotope series reveal additionally to temperature a striking sensitivity to precipitation (mainly for carbon) and sunshine duration (mainly for oxygen) during July and August. A drought index reflecting the combined temperature and precipitation influence provided the most stable correlations over time for the carbon isotope series. All of these climate-isotope relationships are preserved in the isotope series obtained from younger trees at the same site, while strong intertree correlations further emphasize the high climate sensitivity. We thus present the first carbon-isotope-based summer drought reconstruction for the Swiss Alps, which provides new evidence for interannual to long-term changes in summer regional moisture variability from 1650 to 2004 in Europe, revealing extreme drought summers in the second half of the 18th century and throughout the 20th century.