Africa’s groundwater systems lie at the nexus of escalating human water demands and the intensifying impacts of climate change. This necessitates an understanding of projected groundwater recharge, evolving human water use, and their spatio-temporal interactions. This study performs high-resolution simulations to assess the response of potential groundwater recharge (PGWR) to human water use (HWU) across Africa and under two climate scenarios: RCP2.6 (low emissions) and RCP8.5 (high emissions), throughout the 21st century. The findings reveal marked geographical variability in simulated PGWR, with countries such as Sierra Leone, Liberia, Ethiopia, and parts of Central Africa exceeding 400 mm/year recharge, while hyper-arid regions like the Sahara, Kalahari Desert, and Mandera tripoint remain consistently low. Under RCP8.5, a continent-wide decline of 30.9 mm/year (25.1 %) in PGWR is projected from the near future (2015–2044) to the far future (2071–2100), alongside a significant increase in interannual variability. In contrast, RCP2.6 presents a milder trajectory, with continental PGWR declining by only 2.9 mm/year (2.3 %), yet demand continues to rise under both scenarios. HWU increases steadily, particularly under RCP8.5 where the average continental consumption reaches 6.6 mm/year. Domestic water use remains dominant under RCP2.6, while irrigation water use expands significantly under RCP8.5, especially in North Africa. Substantially, the fraction of recharge consumed by humans reaches 35.6 % in North Africa and 12.6 % in West Africa by century’s end. Most notably, 7 countries including Morocco, Algeria, Libya, Egypt, Kenya, Uganda and Nigeria are projected to exploit more than 80 % of simulated local PGWR under RCP8.5, suggesting possible hotspots of unsustainable use and potential groundwater depletion for an estimated projected population of 685 million people (52.9 % African population) by 2045 and 1.031 billion people (72.43 %) by 2100. These results underscore the critical need for proactive, region-specific water governance strategies, particularly in highly stressed regions. Without adaptive intervention, the sustainability of groundwater, which is a cornerstone for drinking water, food production, and ecosystem stability, will be at increasing risk in a warming world.