Abstract: Recent years have witnessed the exacerbated over-extraction of groundwater in the Weihe River basin, leading to a continuous decline in groundwater reserves. To gain a deeper understanding of the spatiotemporal evolution patterns of groundwater levels in a timely manner, this study conducted a systematic analysis of the spatiotemporal distribution and primary influencing factors of changes in the groundwater reserves of the basin using an optimal parameters-based geographic detector (OPGD) and 2002—2024 groundwater storage data determined through inversion of data from the Gravity Recovery and Climate Experiment (GRACE) satellite. The results indicate that the groundwater reserves in the Weihe River basin experienced a periodic increase from 2002 to 2007, followed by a marked decline from 2007 to 2024. The groundwater reserves in the northern part of the basin suffered from the most severe reduction, while those in the central and western portions showed an upward trend. Climatic factors, including precipitation, normalized difference vegetation index (NDVI), and temperature, were considered the primary factors driving groundwater variation, with the q-values of factor detection determined at 0.25, 0.15, and 0.09, respectively. Notably, the interactions between water conservation capacity and climatic factors (especially precipitation and temperature) play a critical role in the groundwater changes observed in the Weihe River basin.