Land use, land cover and climate change (CC) can significantly influence the hydrologic balance and biogeochemical processes of watershed systems. These changes can alter interception, evapotranspiration (ET), infiltration, soil moisture, water balance, and biogeochemical cycling of carbon, nitrogen, and other elements. The need to evaluate the combined effect of land use change and CC of watershed systems is a focus of this study. We simulated watershed processes in the SuAsCo River watershed in MA, USA, using a calibrated and validated Hydrological Simulation Program Fortran model. Climatic scenarios included downscaled regional projections from Global Climate Model models. The Land Transformation Model was used to project land use. Combined change in land cover and climate reduce ET with loss of vegetation. Changes in climate and land cover increase surface runoff significantly by 2100 as well as stream discharge. Combined change in land cover and climate cause 10% increase in peak volume with 7% increase in precipitation and 75% increase in effective impervious area. Climate and land use changes can intensify the water cycle and introduce seasonal changes in watershed systems. Understanding dynamic changes in watershed systems is critical for mitigation and adaptation options. We propose restoration strategies that can increase the resilience of watershed systems.