To explore the cause-effect relationship between river water quality and land use in the basin under extreme weather, this study collected several datasets including land use indexes at multiple spatial scales (1000 m river buffer zone, 500 m riparian buffer zone and sub-basin), water quality data in dry season (November 2019), rainy season-flood season (July 2020) and rainy season-arid season (August 2022). Based on the collected datasets, we explored the effects of land use at multiple spatio-temporal scales on river water quality in the basin, and thus determined the best spatial and temporal scale for protecting water quality and planning land use pattern in the basin and the critical predictors of water quality. Our results showed that the river water quality of the basin was affected by extreme weather. Rainfall would enhance the dilution capacity of the water body. High temperature would accelerate the microorganism reaction rate in the water. The water quality is better in the rainy season-flood season, followed by the rainy season-arid season. The water quality in the dry season is poor. The impact of land use on water quality was affected by both spatial and temporal scales. Land use had the most significant impact on river water quality at the scales of sub-watershed and dry season. Cultivated land, forest land, patch density, largest patch index and edge density were the most significant explanatory variables affecting river water quality. Among them, forest land had a negative correlation with most water quality indicators, while construction land, cultivated land and patch density had a positive correlation with some of the water quality indicators. The results of this study provided a scientific basis for managing land use pattern and protecting river water quality, and was thus important for the sustainable development of human living environment and ecological protection.