ABSTRACT: Water chemistry and the assessment of health risks of potentially toxic elements have important research significance for water resource utilization and human health. However, not enough attention has been paid to the study of surface water environments in many parts of Central Asia. Sixty water samples were collected from the transboundary river basin of Chu-Talas during periods of high and low river flow, and the hydrochemical composition, including major ions and potentially toxic elements (Zn, Pb, Cu, Cr, and As), was used to determine the status of irrigation suitability and risks to human health. The results suggest that major ions in river water throughout the entire basin are mainly affected by water-rock interactions, resulting in the dissolution and weathering of carbonate and silicate rocks. The concentrations of major ions change to some extent with different hydrological periods; however, the hydrochemical type of calcium carbonate remains unchanged. Based on the water-quality assessment, river water in the basin is classified as excellent/good for irrigation. The relationship between potentially toxic elements (Zn, Pb, Cu, Cr, and As) and major ions is basically the same between periods of high and low river flow. There are significant differences between the sources of potentially toxic elements (Zn, Pb, Cu, and As) and major ions; however, Cr may share the same rock source as major ions. The risk assessment revealed low non-carcinogenic and carcinogenic risks for human health; however, the maximum carcinogenic risk for As exceeded the allowable value, which requires further consideration. These results provide a scientific basis for the management of agricultural irrigation uses and also infill existing gaps regarding the hydrochemical composition in the Chu-Talas river basin, Central Asia.