Paleoclimate information is key to understanding the climate system and predicting future climate. Currently, stable isotope analysis of whole molecules in tree rings is among the most advanced paleoclimate tools. Still, it only enables reconstructions of one climate parameter at a time (univariate climate reconstruction), a fundamental limitation. Here, we investigated whether this limitation can be overcome by analysing isotope variability at the level of intramolecular carbon positions in tree-ring glucose. We found that drought governs isotope variability at glucose C-1 to C-3, whereas radiation governs isotope variability at glucose C-5 to C-6. These isotope-climate relationships are statistically and mechanistically robust. According to cross-validation analysis, they can be reconstructed with high accuracy and precision. Thus, intramolecular isotope analysis enables multivariate climate reconstructions (proof of concept).