The impact of climate variability on groundwater storage has received limited attention despite widespread dependence on groundwater as a resource for drinking water, agriculture and industry. Here, we assess the climate anomalies that occurred over Southern Africa (SA) and East Africa, south of the Equator (EASE), during the major El Niño event of 2015–2016, and their associated impacts on groundwater storage, across scales, through analysis of in situ groundwater piezometry and Gravity Recovery and Climate Experiment (GRACE) satellite data. At the continental scale, the El Niño of 2015–2016 was associated with a pronounced dipole of opposing rainfall anomalies over EASE and Southern Africa, north–south of ∼12∘ S, a characteristic pattern of the El Niño–Southern Oscillation (ENSO). Over Southern Africa the most intense drought event in the historical record occurred, based on an analysis of the cross-scale areal intensity of surface water balance anomalies (as represented by the standardised precipitation evapotranspiration index – SPEI), with an estimated return period of at least 200 years and a best estimate of 260 years. Climate risks are changing, and we estimate that anthropogenic warming only (ignoring changes to other climate variables, e.g. precipitation) has approximately doubled the risk of such an extreme SPEI drought event. These surface water balance deficits suppressed groundwater recharge, leading to a substantial groundwater storage decline indicated by both GRACE satellite and piezometric data in the Limpopo basin. Conversely, over EASE during the 2015–2016 El Niño event, anomalously wet conditions were observed with an estimated return period of ∼10 years, likely moderated by the absence of a strongly positive Indian Ocean zonal mode phase. The strong but not extreme rainy season increased groundwater storage, as shown by satellite GRACE data and rising groundwater levels observed at a site in central Tanzania. We note substantial uncertainties in separating groundwater from total water storage in GRACE data and show that consistency between GRACE and piezometric estimates of groundwater storage is apparent when spatial averaging scales are comparable. These results have implications for sustainable and climate-resilient groundwater resource management, including the potential for adaptive strategies, such as managed aquifer recharge during episodic recharge events