Lake Ebinur Basin is an important ecological barrier in Northwest China, maintaining the ecological balance of the region and even the whole northern Xinjiang Province. The water environment of Lake Ebinur Basin is closely related to the local economy and the sustainable development of the basin. However, there are few studies on long-term water quality change, nutritional status and health risk. Therefore, this paper is based on the long time-series monitoring data of 12 sections in Lake Ebinur Basin from 2005 to 2020. The water quality of rivers and lakes was evaluated by the Canadian water quality index (CWQI), the eutrophication status of Lake Ebinur was evaluated by the comprehensive trophic level index (TLI(∑)), and the water environment health risk (WEHR) was evaluated. Combined with stepwise multiple linear regression (SMLR), the relationships between water quality parameters and CWQI, TLI(∑) and WEHR were analyzed. The results show that:(1) The CWQI of Jing River in the lower reaches is larger than that in the upper reaches, while that in Bortala River is opposite, and there is point source pollution both in Jing River and Bortala River. The CWQI of Jing River ranges 46.29-98.71, Bortala River 25.36-99.71, Lake Ebinur 42.29-55.95, respectively, and the coefficient of variation ranges from 0.01 to 0.23; (2) The TLI(∑) of Lake Ebinur from 2005 to 2020 is between mild and moderate eutrophication; the ratio of nitrogen to phosphorus shows that the study area is phosphorus limited; (3) The WEHR in the upper reaches of Jing River is larger than that in the lower reaches, while that in Bortala River is opposite. The health risk of the water environment is mainly affected by chemical carcinogens, As is the most important, followed by Cr⁶⁺. The total risk of each section exceeds the maximum acceptable risk level specified by the United States Environmental Protection Agency (USEPA); (4) Stepwise multiple linear regression analysis showed that COD_Mn, NH₃-N, TP, TN, E. coli, SD (secchi depth) and VP (volatile phenol) affected water quality, COD_Mn, TP and TN affected water eutrophication, and F^-, Cu, As, Cd, Cr⁶⁺, Pb, cyanide and VP affected WEHR. The results of this study can provide a strong scientific basis for the sustainable development of the regional water environment and the rational allocation of water resources.