The discharge of geothermal fluid into the natural water environment may lead to serious damages. In this study, the impact of geothermal waste water on surface water has been investigated in the up-Buyuk Menderes River, Turkey. Thermal return water from district heating and from thermal bath in the Sandikli region were the most important source of major solutes and trace elements to the up-Buyuk Menderes River and tributaries. The thermal contribution causes a drastic increase in Na, SO4 ions, EC, and temperature of surface waters. The concentrations of As, Al, B, Fe, Cr, Li, S, P, Pb, U, Mn, and Zn are increasing dramatically downstream of thermal water inputs in the Kufi Creek tributary. In addition to natural thermal water inputs, water quality was impacted by anthropogenic trace and major element inputs from surface waters. The increased of some trace elements (Al, As, B, Cu, Cd, Fe, Mn, P, U) in surface water are related to anthropogenic activities such as agricultural activities, sewage effluents, and stockyards in the study area. Additionally, surface water quality of the up-Buyuk Menderes River and tributaries was evaluated according to standards given by the Environmental Protection Agency of both Turkey and USA. Our study demonstrates the influence of thermal water inputs on water quality of surface waters.