Based on field monitoring and 3S technology, Qixia city in the low hilly area of Eastern Shandong province was taken as the research area. Pearson correlation, unconstrained PCA and corresponding canonical analysis (CCA) were used to study the coupling between landscape pattern and non-point source pollution at different watershed scales. The results show that: (1) The spatial variation of landscape pattern is obvious; the patches of agricultural land and construction land are relatively fragmented at the characteristic scale; and the patches of other types of land are highly aggregated. (2) The river surface source pollutants in the study area are mainly TN-based, and the main river outlet is the more polluted area. (3) The influence of landscape pattern on water quality during the wet period is greater than that of the normal water period, and TN and EC are most sensitive to the change of land use type area ratio and landscape pattern index. At different scales, water quality affected by landscape pattern and land use type is different. (4) In normal period at riverside scale, landscape that has the greatest impact on TN is the patch density, and EC is most affected by landscape edge density. At small basin scale TN is greatly affected by landscape spread, and COD is closely related to landscape diversity. The diversity of landscape on the scale of the riverbank during the wet period has the greatest influence on TN, the EC is greatly affected by the polymerization of the plaques, and the biggest factors affecting TN on the small basin scale are consistent with the flat water period, and EC is closely related to landscape spread. (5) At small basin landscape, TN is mainly affected by the density of forest land patch, TP and cultivated land dispersion are closely related to the parallel index, the abundance of water TN is significantly influenced by the forest land dispersion and juxtaposition index, TP is sensitive to the change of the average dimensionality of forest land, and EC is most influenced by grassland aggregation. Basically, the study clarified the spatial distribution characteristics of landscape pattern and non-point source pollution in the study area, and discussed the correlation between them at different scales, which provided a scientific basis for sustainable utilization of water and land resources in Qixia city.