Streamflow simulations from the Inter-Sectoral Impact Model Intercomparison Project phase 2b (ISIMIP2b) were analyzed to evaluate future changes in surface water resources over northern Patagonia, a region that contributes significantly to the total hydropower production of Argentina. Ten global hydrological models (GHMs), forced by four general circulation models, effectively capture the winter streamflow maximum in the Negro river basin. However, most of them face challenges in simulating the late-spring pulse due to a misrepresentation of temperature over the higher elevations of the Andes. We quantified the future streamflow evolution using a multi-model ensemble from a subset of the best-performing GHMs under the RCP2.6 and RCP6.0 emission scenarios for two temporal horizons. According to the multi-model ensemble, there is a projected decrease in the annual streamflow of the analyzed rivers, which is more important considering the RCP6.0 scenario during the late 21st century, reaching up to −40% relative to the 1979–2005 reference period. This reduction is attributed to the projected precipitation decline in the headwaters of the Negro river basin in response to changes in the surface pressure patterns. These results have implications for regional water authorities for the development of adaptation plans considering future demand projections.

  • A set of global hydrological models (GHMs) from the ISIMIP2b project was used to characterize streamflow changes in the Comahue region.

  • A decrease in the annual streamflow is projected along the 21st century, particularly for the Neuquén river.

  • Uncertainty is mainly linked to the global climate models used to drive the GHMs.

  • Hydropower generation and irrigation for agriculture are expected to face future reductions.

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