Assessing how climate change will affect hydrological ecosystem services (HES) provision is necessary for long-term planning and requires local comprehensive climate information. In this study, we used SWAT to evaluate the impacts on four HES, natural hazard protection, erosion control regulation and water supply and flow regulation for the Laguna del Sauce catchment in Uruguay. We used downscaled CMIP-5 global climate models for Representative Concentration Pathways (RCP) 2.6, 4.5 and 8.5 projections. We calibrated and validated our SWAT model for the periods 2005–2009 and 2010–2013 based on remote sensed ET data. Monthly NSE and R2 values for calibration and validation were 0.74, 0.64 and 0.79, 0.84, respectively. Our results suggest that climate change will likely negatively affect the water resources of the Laguna del Sauce catchment, especially in the RCP 8.5 scenario. In all RCP scenarios, the catchment is likely to experience a wetting trend, higher temperatures, seasonality shifts and an increase in extreme precipitation events, particularly in frequency and magnitude. This will likely affect water quality provision through runoff and sediment yield inputs, reducing the erosion control HES and likely aggravating eutrophication. Although the amount of water will increase, changes to the hydrological cycle might jeopardize the stability of freshwater supplies and HES on which many people in the south-eastern region of Uruguay depend. Despite streamflow monitoring capacities need to be enhanced to reduce the uncertainty of model results, our findings provide valuable insights for water resources planning in the study area. Hence, water management and monitoring capacities need to be enhanced to reduce the potential negative climate change impacts on HES. The methodological approach presented here, based on satellite ET data can be replicated and adapted to any other place in the world since we employed open-access software and remote sensing data for all the phases of hydrological modelling and HES provision assessment.