The use of pesticides adversely affects the chemical and ecological condition of water resources. The Water Framework Directive (WFD), developed for the conservation and improvement of water resources, is the most current and valid environmental legislation in Europe. WFD aims to achieve a good chemical and ecological status in all water resources. Parameters mainly used to assess chemical and ecological status are respectively priority substances and specific pollutants. Most of the substances classified as priority substances and specific pollutants are pesticides, making them key contaminants according to WFD requirements. The aim of this study is to monitor pesticide residues in the Büyük Menderes River, Turkiye. Monthly samples were collected for the duration of three years, from January 2016 to December 2018, on six different monitoring points. The most frequently detected pesticides in the river water samples were: imidacloprid, acetamiprid, parathion-methyl, dimethoate, metolachlor, clopyralid, carbendazim, and piperonyl butoxide. Since the limit values have been exceeded due to the current pressures in the basin, it is of high importance to take the necessary precautions to prevent the pesticides reaching the body of water.