An accurate quantitative evaluation of anthropogenic effects on regional groundwater dynamics is critical to the rational planning, management, and use of such resources and in maintaining the sustainability of groundwater-dependent ecosystems. Based on groundwater dynamics, a series of groundwater depth evaluation indexes were created to quantitatively evaluate the effects of anthropogenic activities on the groundwater system. These indexes were based on mathematical relationships relating groundwater depth to surface runoff (gammat), precipitation (rhot), and extraction (deltat). The anthropogenic effects on these relationships were evaluated statistically, with respect to both temporal and spatial variation. The anthropogenic effects on groundwater dynamics within the arid Zhangye Basin, located in the middle reaches of northwest China's Heihe River, were investigated. River valley plains in the western portion of the basin excepted, anthropogenic activities have, since 1995, dramatically altered the basin's groundwater dynamics; in particular, in the mid-upper and lower portions of alluvial-diluvial fans and in localized northerly fine-soil plains regions, the relationship of groundwater to surface runoff and atmospheric precipitation has shifted. This and other changes indicate that anthropogenic effects on groundwater systems in this region show clear spatiotemporal variation.