The decrease in freshwater input to the coastal system of the Southern Andes (40–45°S) during the last decades has altered the physicochemical characteristics of the coastal water column, causing significant environmental, social and economic consequences. Considering these impacts, the objectives were to analyze historical severe droughts and their climate drivers, and to evaluate the hydrological impacts of climate change in the intermediate future (2040–2070). Hydrological modelling was performed in the Puelo River basin (41°S) using the Water Evaluation and Planning (WEAP) model. The hydrological response and its uncertainty were compared using different combinations of CMIP projects (n = 2), climate models (n = 5), scenarios (n = 3) and univariate statistical downscaling methods (n = 3). The 90 scenarios projected increases in the duration, hydrological deficit and frequency of severe droughts of varying duration (1 to 6 months). The three downscaling methodologies converged to similar results, with no significant differences between them. In contrast, the hydroclimatic projections obtained with the CMIP6 and CMIP5 models found significant climatic (greater trends in summer and autumn) and hydrological (longer droughts) differences. It is recommended that future climate impact assessments adapt the new simulations as more CMIP6 models become available.