Water quality is a key factor in safeguarding ecosystem functions, protecting human health, and achieving sustainable development. Land use characteristics (including type, intensity, and landscape configuration) serve as important indicators of human activity and have significant impacts on river water quality, which vary across different spatial and temporal scales. This study focuses on the source region of the Chishui River and integrates two spatial scales: riparian buffer and sub-watershed. By applying variation partitioning analysis (VPA) and random forest modeling, we comprehensively quantify the independent and combined contributions of land use type, intensity, and landscape pattern to water quality, while identifying key influencing factors and their corresponding spatial scales. The results show that:① Landscape pattern is the dominant factor affecting water quality (explaining 33–58% of the variation), followed by land use type (11–22%) and intensity (4–16%);② Riparian landscape configuration exerts a more significant influence on water quality, while land use intensity at the sub-watershed scale provides stronger explanatory power;③ The proportion of built-up land, construction intensity (LUI_Con), and agricultural intensity (LUI_Cul) are key predictors of water quality, while forest cover and landscape connectivity play important roles in reducing TN and COD concentrations. These findings suggest that watershed water quality management should consider land use characteristics at multiple scales to identify optimal combinations of riparian and sub-watershed interventions. Specifically, we recommend prioritizing the control of industrial and domestic point-source pollution at the riparian scale, while enhancing agricultural non-point source management at the sub-watershed scale—thus forming an integrated "point-source and non-point source" control system. This study offers new empirical evidence on the multidimensional interactions and scale effects of land use–water quality relationships, providing important theoretical and practical insights for watershed resource protection and spatial planning optimization.