As groundwater found in aquifers is the main reservoir of freshwater for human activity, knowledge of the future response of groundwater to climate change is key for improving water management adaptation plans. We analyse the climate-driven evolution of future levels of unconfined aquifers in the 218 world’s major groundwater basins in global climate simulations following the latest IPCC scenarios, run with models able to capture feedbacks among climate, land use and groundwater. We find a rising of groundwater levels on global average, which is consistent with the projected global intensification of precipitation. However, the evolution of water table depths is not spatially uniform and presents large regional disparities. Depending on the scenario, we find a statistically significant rise (respectively a depletion) of groundwater levels in 2100 over 40[34-47]% to 52[50-54]% (respectively 20[19-24]% to 26[25-29]%) of the area covered by the 218 world’s major groundwater basins. Using spatialiazed projections of population in 2100, we estimate that 31[29-36]% to 43[42-44]% of the world’s population could be affected by these groundwater changes, facing either water scarcity issues, or increased risks of flooding. As the climate models we used do not represent human groundwater withdrawals (irrigation as well as domestic and industrial uses), we also use FAO maps of present-day irrigated areas and projections of population to identify regions where groundwater withdrawals could exacerbate the projected depletion, or even reverse a projected rise into a depletion.