Present and prospective climate change will likely affect the hydrological cycle in sensitive areas, such as the Alps, thus impacting water-based activities. A most representative example is hydropower production, i.e., exploitation of water to produce energy. In the Italian Alps hydropower is strictly dependent upon water from snow and ice melt, and both are decreasing in response to global warming. Here, we study the effects of potential climate change scenarios at 2100 upon hydropower production from the Chavonne plant, in Valle d’Aosta region of Italy, a run-of-the-river (ROR) plant taking water from two high altitude glacierized catchments of Val di Cogne, and Valsavarenche. We use Poli-Hydro, a state-of-the-art hydrological model to mimic the hydrological budget of the area, including ice and snow melt share. Projections of the hydrological budget were built until 2100 by means of selected climate change scenarios, under proper downscaling. We used runs of three General Circulation Models (GCMs), EC-Earth, CCSM4, and ECHAM6.0 under three Representative Concentration Pathways RCP 2.6, RCP 4.5, and RCP 8.5 from AR5 of IPCC, and of their updated version under four Shared Socio-Economic Pathways SSP1 2.6, SSP2 4.5, SSP3 7.0, and SSP5 8.5 from AR6. We then assessed hydropower production changes against a recent control run CR period (2005–2015). Mean annual flow is estimated at 14.33 m3 s−1 during CR, with ice melt contribution ca. 2%, and snow melt contribution ca. 44%. Ice cover in 2005 was estimated as 19.2 km2, reaching in 2015, 9.93 km2. Mean hydropower production was estimated at 153.72 GWh during the CR. Temperature would largely increase throughout the century (+0.93 °C on average at the half century, +2.45 °C at the end of the century). The ice covered area would be largely depleted (ca. −86%, −94% respectively), with reduced contribution of ice melt (0.23%, <0.1%, respectively) and snow melt (ca. 37%, 33%, respectively). Precipitation would show uncertain patterns, and hence incoming discharge at the plant would erratically vary (−29% to +24% half century, −27% to +59% end of century). Hydropower production displays a large dependence upon monthly discharge patterns, with mostly positive variations (+2.90% on average at half century, +6.95% on average at end of century), with its change driven by exceedance of plant’s capacity.