Important for irrigation, the transboundary river basin between Kyrgyzstan and Kazakhstan is vulnerable to geochemical and anthropogenic sources of pollution. The use of water use indices, together with measurements of the elemental and radionuclide composition of the water and bottom sediments, provides a means for evaluating the continued use of the water from this region. Recent monitoring shows the highest concentrations of hazardous contaminants include lead and thorium contained in the bottom and banks of the Kichi-Kemin River. These contaminants are likely remnants of an accidental spill at the Aktyuz tailing dump in 1964. The specific activity of the Th-232 of the bottom and banks of the Kichi-Kemin River is 107–189 Bq/kg. There is evidence of anthropogenic sources of additional pollution from uranium in both the bottom sediments and the water in the Oyrandy River. The geochemical origins of uranium and other associated elements in the water of the Shu River are likely the Kamyshanovskoye deposit. Contact between the riverbed and ore bodies in this region likely leads to elevated concentrations of several geogenic contaminants, including lithium, strontium, uranium, and boron (Li, Sr, U, B), increasing by as much as 60–130%. The uranium concentrations in the water of channels that are used for irrigation exceed the maximum allowable contaminant levels by 3.8 times. Future work is needed to evaluate the ecological and human health impacts of these contaminants in irrigation and drinking water.