Nossana represents an important pre-Alpine karst spring for drinking supply, sustaining a water distribution system serving 300,000 people. The goal of this study was to project Nossana discharges and evaluate potential supply limits for four future periods (2021–2040, 2041–2060, 2061–2080, 2081–2100). Bias-corrected Regional Climate Models (RCMs), part of the EURO-CORDEX experiment and forced by three emission scenarios (RCP2.6, RCP4.5, RCP8.5), were evaluated, statistically downscaled, and used as input in a calibrated rainfall-runoff model ensemble. For each emission scenario, the calibrated model ensemble considered three RCMs and ten rainfall-runoff parameterizations. Projected ensemble mean discharges are lower than observations (3%–23%) for all RCPs, though they do not show a clear trend between the four time periods. Days characterized by discharges lower than actual water demand are projected to decrease, except for the RCP8.5 emission scenarios and the period 2081–2100. Conversely, the same consecutive days are expected to increase after 2060 for all emission scenarios. These results reflect the projected precipitation trend, characterized by longer, drier summer periods and wetter autumns in comparison to today’s climate. Also, they indicate a possible need for alternative drinking water resources. The proposed methodology was demonstrated to deliver useful quantitative information for water management in the mid- long-term period.