Abstract: Clarifying the variation law of water quality in the main stream of the Three Gorges Reservoir after impoundment can provide a reference for water environment protection and management in the reservoir area. Based on the monthly water quality data of multiple sections of the mainstream of the reservoir area from 2004 to 2019, this paper uses Mann-Kendall test method, water quality index（WQI） comprehensive evaluation method and cluster analysis to analyze and study ten typical water quality indicators. The results show that since the impoundment of the Three Gorges Reservoir, the annual average concentration of permanganate index, five-day biochemical oxygen demand, ammonia nitrogen and lead in each section of the main stream of the reservoir area have all met the Class Ⅲ water quality standards, and the water quality in the reservoir area has generally improved. According to the inter-annual fluctuation characteristics of water quality indicators, it can be divided into three time stages: 2004-2006,2007-2014 and 2015-2019, and the spatial heterogeneity of each stage is different. The concentration of total nitrogen in each section of the reservoir mainstream ranged from 1.3～2.1 mg/L, and the concentration of fecal Escherichia coli group in the section of Cuntan and Qingxichang is 10 735～79 000 A/L, which exceeds the Class Ⅲ water quality standard as the main pollution index of the reservoir mainstream. The water quality of the Cuntan section is the worst among the six sections, which needs to be paid attention to. The water storage and sediment retention effect of Xiluodu-Xiangjiaba cascade reservoirs in the upper reaches of the Yangtze River will reduce the inflow pollutant flux of the Three Gorges Reservoir and improve the water quality of the mainstream of the reservoir area. The water level rise during the impoundment of the Three Gorges Reservoir by stages is conducive to the improvement of water quality in the reservoir area. The regular operation during the year affects the annual change of water quality in the mainstream of the reservoir area. The water quality law of the section located in the fluctuating backwater area is different from that in the perennial backwater area.