Quaking aspen, Populus tremuloides, has experienced severe declines in recent years in part due to the effects of changing climate and extreme drought. This study set out to investigate these effects by assessing associations of climatic, edaphic and topographic variables with physiological drought stress in aspen. The study took place on the Zumwalt Prairie in northeastern Oregon, a semi-arid bunchgrass prairie where aspen occur in isolated stands associated with riparian areas and late-season persistence of snow drifts. Using a 33-year time series of Landsat imagery to detect associations of aspen stands late-season snow cover and field measurements of soil moisture in aspen stands during 2017, we found while snow dominated stands were associated with greater soil moisture during spring, levels had equilibrated to those of other upland stands by summer. Measurements of predawn and midday stem Ψ in multiple height classes of aspen ramets revealed associations of both shallow soil moisture and vapor pressure deficit with physiological drought stress in aspen. Analysis of soil texture class revealed an important association with midday stem Ψ, with finer textured soils associated with decreased stem Ψ in comparison to coarser textured soils. While neither topographical characteristics nor snow cover were found to be important drivers of drought stress, topographical curvature was found to have a strong influence on summer soil moisture in upland stands. These findings contribute to our understanding of aspen physiology, drought ecology and landscape hydrology toward the xeric margin of aspen’s range. This information can help land managers anticipate and adapt to changing climates and understand their effects on key plant species such as aspen.