There is great uncertainty about the future effects of climate change on the global economic, social, environmental, and water sectors. This paper focuses on watershed vulnerabilities to climate change by coupling a distributed hydrological model with artificial neural networks and spatially distributed indicators for the use of a predictive model of such vulnerability. The analyses are complemented by a Monte Carlo evaluation of the uncertainty associated with the projections of the global circulation models, including how such uncertainty impacts the vulnerability forecast. To test the proposal, the paper uses current and future vulnerabilities of the Turbio River watershed, located in the semi-arid zone of Guanajuato (Mexico). The results show that nearly 50% of the watershed currently has medium and high vulnerabilities, and only the natural areas in the watershed show low vulnerabilities. In the future, an increase from medium to high vulnerability is expected to occur in urban and agricultural areas of the basin, with an associated uncertainty of ±15 mm in the projected precipitation.