Analysis of the state of water resources in Ukraine provides an opportunity to improve the ecological situation on the basis of hydrographic and water management zoning using the latest methodological approaches and technologies for constructing the water balance of the basin areas. The aim of the research is to establish patterns of change in the quality indicators of the country's water resources in the largest basin of the Dnipro River. The study was carried out on the basis of an assessment of indicators for monitoring changes in the quantitative and qualitative indicators of water resources in the Dnipro basin in 2016-2021.A decrease in the Dnipro runoff was recorded: the average long-term natural runoff at the mouth is 53.3 km3, and the actual runoff is about 11 km3 (20%) less than the natural runoff. A decrease in the quantitative indicators of water intake from the Dnipro basin in 7365 million m3, a decrease in the quantity (up to 547.1 million m3) and a deterioration in the quality of return water and the general state of water resources in the basin from the northwest to the southeast. The measurements’ results of the indicators of the waters’ qualitative state in the reservoirs and the main watercourses of the basin at the locations of the monitoring points indicate that the norms are exceeded by a multiplicity of more than 5 times, including in terms of BOD and COD, which reflect the intensity of pollution of water bodies with easily oxidizing and difficult oxidizing organic compounds. The screening of pollutants revealed the content of pesticides, drugs, antidepressants, heavy metals-carcinogens in the Dnipro water, which makes it possible to investigate the problems with water resources, taking into account the specifics of the river basin. Such an assessment shows that climate change and industrial enterprises, as notable anthropogenic component, are significant factors affecting water resources. This indicates the importance of the direction of the policy of state regulation on water monitoring, the introduction of an irrigation and drainage strategy, the construction of centralized water supply and sanitation systems and strict control over the indicators of wastewater discharge.