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Groundwater is an important source of water supply and ecosystem resilience. However, limited information on spatio-temporal dynamics makes a complete assessment of available groundwater resources difficult, impairing sustainable water management. The Gravity Recovery and Climate Experiment mission (GRACE) has recently made this possible. In this study, we used the Yellow River Basin (YRB) as a model system to explore the use of spatio-temporal dynamics information about groundwater change derived from the GRACE datasets for regional groundwater management. While there was an overall decreasing trend (R-2 = 0.57) during the last 14 year, the groundwater storage over the whole basin decreased significantly (p < 0.0001, slope changed from - 0.0137 cm/month to - 0.0684 cm/month) since 2010 (2010-2016) and showed stronger fluctuations than the time before (2003-2009). The range and the standard deviation of groundwater storage change also increased in recent years especially after 2010. At the basin scale, locations which exhibited higher variabilities (large standard deviation) over time generally showed radical decrease of groundwater storage. The results indicated that groundwater depletion may reduce the aquifers' function for ecosystem resilience, thus posing risks to the ecosystem of the YRB and threatening its people to climate change and extreme events. Despite the overall trend, the changes were heterogeneous if looking at finer scales: spatially, there was a gradual decline of storage from west to east (e.g. the change in December 2016 was - 3.6, - 9.1 and - 25.8 cm for the upper, middle and lower reach, respectively); and temporally, the timeseries among the reaches were significantly different (p = 0.023). Our hotspot analysis also indicated the heterogeneity in groundwater decline across the basin and through the time. Additionally, it showed that human factors (e.g. groundwater consumption) become dominant in determining the groundwater change pattern over climatic variations. We therefore call for more attention to groundwater in developing sustainable water management strategies and suggest a closer cooperation of neighboring provinces in the YRB to have a reciprocal strategic plan for water regulation, protection, and management.