Groundwater sustains human well-being and ecosystems functioning. Many regions in Europe have experienced declining groundwater levels caused by decreasing groundwater recharge (GWR) or increasing groundwater abstractions (GWAs). These changes can lead to groundwater-related stress, threatening ecosystems and water supplies. Existing groundwater stress indicators estimate stress during a given period but do not address how stress changes or show the uncertainty of future stress. We propose a novel indicator of future groundwater stress (GWSI) due to changes in GWR and GWA and, thus, the alteration of long-term mean annual groundwater discharge (GWD). Groundwater stress is defined as any alteration in GWD since ecosystems are adapted to an equilibrium state. Focusing on decreasing GWD, which is generally more harmful than increasing GWD, we quantified the future GWSI in Europe by integrating scenarios of GWR and GWA in 2070–2099. GWR was evaluated using an ISIMIP2b multi-model ensemble of eight global hydrological models driven by the output of four global climate models under two greenhouse gas emission scenarios. GWA scenarios for irrigation, domestic and manufacturing sectors were combined with the GWR projections to generate an ensemble of GWSIs, simplified into three groundwater stress scenarios (high, intermediate, low). Projected GWSIs vary significantly among the scenarios. For the high-stress scenario, 58% of Europe’s land area is projected to experience a GWD decrease of at least 25% under RCP8.5 compared to 38% under RCP2.6, while the respective values are 26 and 1% for the intermediate-stress scenario. Groundwater demand management alone might not prevent GWD declines under the high-stress and intermediate scenarios, particularly under RCP8.5. Therefore, climate change mitigation might imperative for reducing the decline of GWD, especially in Eastern and Southeastern Europe, where changes in GWR are projected to be the primary cause of declining GWD (in the high abstraction scenario under RCP8.5). Under RCP2.6, reductions in GWAs by 25–75% might balance a GWD decline in parts of Spain and Italy where GWAs are high, even in the high-stress scenario. In line with the precautionary principle, we recommend adapting to the high-stress scenario to minimize harm to the beneficiaries of groundwater.