Trees continuously regulate leaf physiology to acquire CO2 while simultaneously avoiding excessive water loss. The balance between these two processes, or water use efficiency (WUE), is fundamentally important to understanding changes in carbon uptake and transpiration from the leaf to the globe under environmental change. While increasing atmospheric CO2 (iCO2 ) is known to increase tree intrinsic water use efficiency (iWUE), less clear are the additional impacts of climate and acidic air pollution and how they vary by tree species. Here, we couple annually resolved long-term records of tree-ring carbon isotope signatures with leaf physiological measurements of Quercus rubra (Quru) and Liriodendron tulipifera (Litu) at four study locations spanning nearly 100 km in the eastern United States to reconstruct historical iWUE, net photosynthesis (Anet ), and stomatal conductance to water (gs ) since 1940. We first show 16%-25% increases in tree iWUE since the mid-20th century, primarily driven by iCO2 , but also document the individual and interactive effects of nitrogen (NOx ) and sulfur (SO2 ) air pollution overwhelming climate. We find evidence for Quru leaf gas exchange being less tightly regulated than Litu through an analysis of isotope-derived leaf internal CO2 (Ci ), particularly in wetter, recent years. Modeled estimates of seasonally integrated Anet and gs revealed a 43%-50% stimulation of Anet was responsible for increasing iWUE in both tree species throughout 79%-86% of the chronologies with reductions in gs attributable to the remaining 14%-21%, building upon a growing body of literature documenting stimulated Anet overwhelming reductions in gs as a primary mechanism of increasing iWUE of trees. Finally, our results underscore the importance of considering air pollution, which remains a major environmental issue in many areas of the world, alongside climate in the interpretation of leaf physiology derived from tree rings.