Nen River flows through Inner Mongolia, Heilongjiang and Jilin Provinces, which form the neighboring sections at the border of the provinces. In this study, 10 water parameters covering 11 sites were detected from 2011 to 2015. Cluster analysis (CA) was used to assess the spatial variation of Nen River, and grouped 11 sampling sites into three clusters (low, moderate and high pollution). Nen River was more highly influenced by the tributary of Yin River. Along the mainstream of Nen River, the water quality downstream was worse than upriver. The major pollution sources were agricultural activity, industrial drainage and city populations. With government management, the point source pollution upstream was well controlled, and the water quality of Nen River improved obviously in 2015. Grey relational analysis (GRA) combined with principal component analysis (PCA) and pairwise correlation analysis showed NH4+-N and total phosphate (TP) were principal factors influencing the water quality of Nen River. The TP in most sites of Nen River was still in high concentration (higher than 0.1 mg L–1). It was mainly caused by nonpoint source pollution that should be effectively measured in the future. This is the first time the water quality of the neighboring sections along Nen River has been assessed.