To investigate the response of water quality to land use and landscape pattern of different scales, this study analyzed the spatial and temporal heterogeneity of water quality and the characteristics of land use and landscape patterns in multi-scale riparian buffer zones based on the hydrological and water quality data of seven transects in the Three Gorges Reservoir area from 2019 to 2021 and the land use data in 2020. Correlation analysis and redundancy analysis (RDA) were also used to determine the effects of land use and landscape patterns on water quality indicators and the optimal scale of influence. Then, partial least squares regression (PLSR) was used to explore the key influencing factors under the optimal scale of influence. The results show that the overall water quality condition in the Three Gorges Reservoir area was stable, the water quality in the dry water period was better than that in the wet period, and the water quality condition was mainly affected by non-point source pollution, tributary confluence, the phosphorus industry and urbanization. Furthermore, the landscape patches in the small-scale buffer zone were severely fragmented, but more diversified; cultivated land was the dominant landscape type in the reservoir area, and its increased fragmentation was conducive to improving the aquatic environment; forest and grassland had a better purifying effect on the water environment in the dry period than in the wet period, whereas waters were the main source of nitrogen and phosphorus pollutants in the river. Generally, the explanatory ability of land use and landscape patterns on water quality indicators was higher in the wet period than in the dry period, and was strongest on the 300 m buffer scale, where cultivated land, grassland, waters and patch density (PD) were the key variables influencing the water quality indicators.