Land use in uplands is an important factor affecting water quality in its respective catchment, and its influences at the different spatial scales and configurations warrant further investigation. Here, we selected 26 catchments in the upper Han River (China) and sampled the surface water at the outlet of each catchment in four seasons during 2019. Multivariate statistics were used to identify the relationships between land use characteristics in uplands and water quality in river system. The results indicated that chemical oxygen demand (CODMn); pH; dissolved oxygen; electrical conductivity; nutrient, i.e., NH4+–N, NO3−–N; and dissolved phosphorus (DP) in rivers displayed significant seasonal variations. Stepwise regression revealed that landscape metrics such as patch density, landscape shape index, and splitting index were important factors influencing water quality in rivers regardless of their spatiality and seasonality. Urban was the most frequently chosen land-use type in the best prediction models, and forest area showed a negative correlation with water quality parameters in most cases for example, DP. Overall, the influence of land use on river water quality was slightly stronger at reach scale than at catchment and riparian scales. Also, nutrients (i.e., NH4+–N, NO3−–N, and DP) in rivers were primarily impacted by the land use characteristic at catchment and riparian scales. Our results suggested that multi-scale explorations would help to achieve a fully understanding on the impacts of land use on river water quality.