Climate change and increases in human activities are threatening water availability in the Arequipa Region (southern Peru). However, to date, there has not been a comprehensive inventory of surface water data or an investigation of current surface water conditions or forecasted future conditions resulting from increased anthropic demand or stresses from climate change. This study evaluates surface water resources management including storage, diversions, and conveyance in the Arequipa Region, while creating a tool for the evaluation of future scenarios in the five main watersheds of this arid region of southern Peru. State-of-the art, open-source modeling software was used. Water uses for each watershed were evaluated against predicted reservoir inflows and streamflows for different periods. In addition to the above, 12 climate change models and different shared socioeconomic pathways (SSP) were ensembled for the five watersheds. A semi-distributed approach and an innovative simulation splitting approach was used for each watershed, which allowed for different starting dates for the simulations using all available data obtained from different sources (government and private). Results indicate that the region is expected to have increased flows during the wet season and no significant changes during the dry season. Reservoir inflows are expected to increase up to 42 and 216% for the lowest and highest SSP evaluated, respectively. Similarly, the model projected streamflow increases up to 295 and 704%, respectively. Regarding yearly water availability and considering current and future demands for the watersheds under study, water deficits are not expected in the future if current reservoir storage can be maintained, though it is expected that reservoirs won’t be able to store predicted higher flows, so important volumes of water could be lost during the wet season to the ocean by natural drainage. Given the uncertainty of climate change projections, if future water sustainability is desired, storage and irrigation efficiencies should be improved and reservoir sedimentation should be evaluated.