The object of the study is the Amudarya River, which is the only source of water supply and domestic water use of the population of the Republic of Karakalpakstan. The studies were carried out because the Republic of Karakalpakstan belongs to the regions of ecological disaster. Therefore, work to reduce anthropogenic pollution's adverse impact on the environment is necessary. The research methods included the sampling of water from the Amudarya River in the established sections of the reservoir according to the seasons of the year for five years, 2016-2020, and the conduct of water analysis following the standard O'zDSt 951:2011 “Sources of centralized domestic and drinking water supply. Hygienic, technical requirements, and selection rules. The indicators of taste, smell, and water color in the studied sections of the Amudarya River correspond to the established hygienic standards. The concentrations of ammonium, nitrates, nitrites, sulfates, chlorides, and total iron in water do not exceed their maximum allowable concentrations. However, the concentrations of turbidity, total hardness, and mineralization of water exceed the permissible values set on them. The maximum turbidity concentrations in water are 39.0 mg/l, total hardness 10.8 mg-eq/l, and salinity 1182.0 mg/l. Based on the work results, monitoring of water quality in the Amudarya River in Karakalpakstan has been improved. This research aimed to study the long-term quality and assessment of water in the Amudarya River in the territory of Karakalpakstan.