Blackening and odorization of heavily polluted rivers has become a serious concern and threat to ecological and human health. This paper aims to gain a deeper understanding of changes in water pollution and the cause of pollution formation in a heavily polluted river in the upper Hai River. In this study, comprehensive water quality index (CWQI) and multivariate statistical techniques (MSTs) were applied to assess the spatiotemporal variation characteristics of water pollution and to identify potential pollution sources. The seasonal Mann–Kendall (SMK) test and the SMK test of flow-adjusted concentrations were effectively used to explore the temporal variation trends of major pollutants and the causes of their formation. Data of 15 water quality parameters were analyzed during 1980–2018 at 19 monitoring sites in the mainstream and major tributaries of the Xinxiang Section of the Wei River (XSWR). The results showed that the rivers were seriously polluted from 1991 to 2009, but the water quality improved after 2010. Nineteen sampling sites were divided into a low pollution region and a high pollution region. In the flood season, the pollution sources were mainly domestic sewage, industrial wastewater, agricultural runoff, biochemical pollution, and natural sources. In the nonflood season, the pollution sources were mainly domestic sewage and industrial wastewater. In recent years, the water quality of seriously polluted river has generally improved, mainly due to reductions in pollutant discharge from point sources and nonpoint sources.