Quaking aspen, Populus tremuloides, has experienced severe declines in recent years in part due to the effects of changing climate and extreme drought. As the dominant deciduous tree in Western North American forests, aspen plays a critical role in forest biodiversity and ecosystem function. Therefore, the persistence of this species under changing climate patterns is a topic of critical concern; especially where aspen exists toward the vulnerable margin of its range. This study set out to investigate the associations of atmospheric, hydrologic, 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 water potential 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 water potential, with finer textured soils associated with somewhat higher midday drought stress than 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 to anticipate and adapt to changing climates and understand their effects on key plant species such as aspen.