The spatio-temporal complexity of groundwater storage change is a result of interconnected impact of socio-ecological factors. Previous research indicates several socio-ecological factors (e.g. human extraction, land cover change, and climate change) that may result in groundwater depletion. However, we seldom have empirical studies that provide spatio-temporally explicit information on the main drivers among these factors that determine regional groundwater change. This research explored a spatio-temporally explicit understanding on the socio-ecological determinants on the changes of groundwater storage in the Yellow River Basin (YRB) of north China. We selected this basin because the spatial heterogeneity of this basin complicates the relationship between socio-ecological factors and groundwater resources, whose changes would in turn fundamentally affect the socio-ecological system in the YRB. We collected annual (time resolution) data between 2003 and 2016 (time scope) with 1° × 1° grid (space resolution) about 18 social-ecological factors that might affect groundwater storage change in the YRB (space scope). Using this data and groundwater storage information from Gravity Recovery and Climate Experiment database, we determined best predictors, highly-performed predictive models, and dominant drivers for temporal and spatial changes of groundwater storage. Temporal changes of groundwater in the YRB between 2003 and 2016 were mainly contributed by anthropogenic factors, including population density, plantation, and irrigation water consumption over time. The spatial groundwater change across the YRB was determined by both the geographical location (e.g. indicated by longitude) and urbanization level (e.g. indicated by the domestic and industrial water consumption). The knowledge about socio-ecological determinants on groundwater dynamics in space and time in the YRB can help determine main levers to control regional change of groundwater storage and assist in a sustainable use of groundwater resource. Display omitted •We identified predictors and determinants of groundwater change in the Yellow River Basin (YRB).•We developed predictive models for spatio-temporal changes of groundwater storage in the YRB.•Anthropogenic factors dominated temporal changes of groundwater in the YRB between 2003 and 2016.•Nature and human collectively determined the spatial changes of groundwater in the YRB.