To determine the spatiotemporal distributions and human health risks of fluoride and arsenic in the rivers of Kyrgyzstan as influenced by mining and other industries, 169 water samples were collected from the main rivers and tributaries of Kyrgyzstan from 2016 to 2018. Through the use of cold and hot spot analysis, multivariate statistical analysis and health risk assessment model, the results indicated that the fluorine and arsenic concentrations in river waters increased year by year from 2016 to 2018. In total, 2.38%, 3.26% and 10.64% of the analyzed samples exceeded the drinking water standard of a maximum permissible limit of 1 mg/L for fluoride, and 0%, 1.09% and 2.13% of the samples exceeded the limit of 10 µg/L for arsenic in 2016, 2017 and 2018, respectively. The gathering areas for high fluorine concentrations were mainly distributed in the Issyk-Kul Basin, Chu River Valley and Fergana Basin, and the gathering areas for high arsenic concentrations were mainly concentrated in the Chu River Valley and southern Fergana Basin. Although fluorine and arsenic were not found to exceed the limits simultaneously, the two pollutants accumulated high values in the southern Fergana Basin in 2018, which indicated the risk of joint poisoning. The distributions of high fluorine and arsenic were found to be determined by mining, industrial and agricultural activities, but not by natural sources. From 2016 to 2018, arsenic concentrations in the river water of Kyrgyzstan created a high risk of carcinogenesis by the ingestion intake exposure route, which resulted in the total risk of health hazards to children and adults caused by fluoride and arsenic to exceed the maximum acceptable ranges. Therefore, further monitoring and management are urgently needed.