With rapid social and economic development, land use/land cover change (LUCC) has intensified with serious impacts on water quality in the watershed. In this study, we took Dongjiang Lake watershed as the study area and obtained measured data on water quality parameters from the watershed’s water quality monitoring stations. Based on Landsat-5, Landsat-8, or Sentinel-2 remote sensing data for multiple periods per year between 1992 and 2022, the sensitive satellite bands or band combinations of each water quality parameter were determined. The Random Forest method was used to classify the land use types in the watershed into six categories, and the area proportion of each type was calculated. We established machine learning regression models and polynomial regression models with WQI as the dependent variable and the area proportion of each land use type as the independent variable. Accuracy test results showed that, among them, the quadratic cubic polynomial regression model with grassland, forest land, construction land, and unused land as its independent variables was the best model for coupling watershed water quality with LUCC. This study’s results provide a scientific basis for monitoring spatial and temporal changes in water quality caused by LUCC in the Dongjiang Lake watershed.