Protecting the water quality of the Yellow River is of great significance to the ecological protection of the Yellow River Basin. The identification of spatiotemporal variations of the water environment and the implementation of measures to control non-point source (NPS) pollution are both key to improving the water quality. Between 2012 and 2021, we conducted assessments of eight indicators, including water temperature, dissolved oxygen (DO) and pH, chemical oxygen demand (CODMn), five-day biological oxygen demand (BOD5), total phosphorus (TP), NO3-N, and NH3-N at six sites in the main stream of the Yellow River in Henan. We explored the causes of changes in water eutrophication using multivariate statistical analysis and formulated recommendations to improve NPS pollution through adjustments in land use patterns. The results showed that temporal water eutrophication markedly decreased and it was most spatially severe in the east. The most effective control of water eutrophication was observed between 2016 and 2018. As the transition from the flood season to the non-flood season took place, the main source of NPS pollution changed from being primarily influenced by precipitation, to being predominantly attributed to agricultural runoff. We recommend addressing the increased soil erosion in the west and controlling the discharge of agricultural effluent in the east. During the flood season, the ecological interception zones can effectively intercept NPS pollution outputs. These findings offer valuable insights for future scientific management strategies to prevent and control NPS pollution in the river.