The intensive use of water resources and the transformation of natural landscapes under the influence of human economic activity have led to changes in the natural water balance of river drainage basins. The negative processes thereof are intensified by climatic changes that have significantly disturbed the hydrological regime, determined by changes in water content and river flow dynamics. The retrospective study and prediction of the flow of the Dnieper River was carried out using multivariate statistics and adaptive methods of nonlinear time series analysis. The anomalous features were identified and the main periods of changes in the water regime of the river for 190 years (1818-2008) were determined using the standard root-mean-square deviation and wavelet analysis. As a result of non-linear prediction, it was determined that if the tendency of anthropogenic and climatic formation of the water regime of the Dnieper River sustains, there is a 90% probability of insignificant but steady trend and cyclical reduction of the average annual flow by 1.6 m3/s per year to 1120 ± 270 m3/s by 2040. The results of the detailed retrospective analysis for 190 years and the prediction of the probability of changes in the flow of the Dnieper river confirm the previous conclusions of many scientists regarding the significant transformation of the ecosystem of the transboundary river and provide new knowledge regarding the main stages of formation of the water regime and the probability of further regulation of the flow of the Dnieper river if the current conditions of the negative impact of economic activities are maintained in the transboundary basin.