In recent decades, climate change has influenced the quantity and quality of water resources, affecting water supply for various demands. In this case study, the effects of climate change on the quality of the Ardak River in the northeast of Iran are discussed. The Qual2kW model was used to simulate water quality parameters, by sampling dissolved oxygen (DO), pH, chemical oxygen demand (COD), and NO3. The rainfall-streamflow model IHACRES was used for simulating monthly streamflow. Monthly general circulation model (GCM) temperature and rainfall data from representative concentration pathways (RCP) RCP2.6 and RCP8.5 were downloaded for 1986 to 2005 and 2020 to 2039. The previously verified model LARS-WG was used to predict future temperatures and rainfall. By importing this data into IHACRES, stream flows were simulated, enabling Qual2kW to predict future effects on water quality. Although changes in temperature of 0.5 to 1.2 °C were predicted, maximum changes in temperature and rainfall will occur in winter and summer in series. Therefore, water quality was predicted to decrease only on the Abghad branch, due to increased temperature and lower flow rates. The highest percentage variations in DO and NO3 are −12.19 and 31.25 in RCP8.5 and in COD and PH, −35.4 and 0.29 in RCP2.6.