Landscape patterns in a watershed potentially have significant influence on the occurrence, migration, and transformation of pollutants, such as nitrogen (N) and phosphorus (P) in rivers. Human activities can accelerate the pollution and complicate the problem especially in a peri-urban watershed with different types of land use. To characterize the heterogeneous correlations between landscape patterns and seasonal variations of N and P in a peri-urban watershed located upstream of Tianjin metropolis, China, observations of total nitrogen (TN) and total phosphorus (TP) at 33 locations were performed in the wet and dry seasons from 2013 to 2016. The data from individual locations were averaged for the wet and dry seasons and analyzed with geographical detector to identify influential landscape indices on seasonal water quality variations. The geographically weighted regression method, capable of analyzing heterogeneous correlations, was used to evaluate the integrated effects from different landscape indices. The results demonstrated that the location-weighted landscape contrast index (LWLI), the ratio of urban areas, and the ratio of forest areas were major influential indicators that affected TN and TP in river water. These indices also had integrated effects on variations of TN and TP together with other indices such as Shannon diversity index, landscape shape index, largest patch index, and contagion index. The integrated effects were different in the wet and dry seasons because of different effects of flushing and dilution by rainwater and the heterogeneity in landscape patterns. The LWLI had a positive relationship to water quality in the areas with high ratio of urban areas, indicating that domestic wastewater can be a major source of N and P pollution. The approaches and findings of this study may provide a reference for characterizing the major factors and integrated effects that control nonpoint source pollution in a watershed.