The Gediz Basin is a Mediterranean watershed along the Aegean coast of Turkey, in which the most important economic activity is agriculture. Over the last few decades, this basin has been experiencing water-related problems such as water scarcity and competing use of water. This study assesses the impact of future climate change on the availability of water resources in the Gediz Basin during the 21st century by investigating the inflows into the major reservoir in the basin, Demirkopru Reservoir, which is the major source of irrigation water to the basin. The analysis in this study involves setting up a coupled hydro-climate model over the Gediz Basin by coupling the Weather Research and Forecasting (WRF) model to the physically-based Watershed Environmental Hydrology (WEHY) model. First, the WRF model is used to reconstruct the historical climatic variables over the basin by dynamically downscaling the ERA-Interim reanalysis dataset. The calibrated and validated WRF model is then used to dynamically downscale eight different future climate projections over the Gediz Basin to a much finer resolution (6 km), which is more appropriate for the hydrologic modeling of the basin. These climate projections are from four Coupled Model Intercomparison Project Phase 5 (CMIP5) Global Climate Models (GCMs), namely, CCSM4, GFDL-ESM2M, HadGEM2-ES, and MIROC5, under two IPCC (The Intergovernmental Panel on Climate Change) representative concentration pathway scenarios (RCP4.5 and RCP8.5). The outputs from the WRF model are then input into the WEHY model, which is calibrated and validated over the basin, to simulate the hydrological processes within the basin and to obtain the projected future inflows into the Demirkopru Reservoir. Results of the future analysis over the 21st century (2017–2100) are then compared to the historical values (1985–2012) to investigate the impacts of future climate change on the hydroclimatology of the Gediz Basin.