Understanding of how changes in diverse human activities and climate contribute to water quality dynamics is crucial for sustainable water environment management especially in the arid and semi-arid regions. This study conducted a comprehensive estimation of the surface water quality change in the Yellow River basin during 2003-2017 and its responses to varied pollution sources and water volumes under socioeconomic and environmental influences. Basin-wide measurements of chemical oxygen demand (COD), ammonium nitrogen (NH+4-N) and dissolved oxygen (DO) concentrations were used in trend detection. Annual anthropogenic (covering six sectors) and natural (sediment-induced, flow-in from the upstream and stored last year) pollution sources and water components (inflow, natural runoff, water consumption, reservoir storage and evaporation) were compiled for each sub-basin. Bottom-up hierarchical analysis was then performed to differentiate individual contributions. Results showed significant decreasing trends in COD and NH+4-N concentrations and increasing trends in DO concentrations. The middle reaches that traverse the Loess Plateau however remained severely polluted with 11.3-39.0% inferior to level III in 2017. The pollutant load played major positive contributions that gradually increased from upper to lower reaches. Declines in urban, rural and industrial pollution discharges following environmental investments and rural depopulation contributed the most: 78-96% for COD and 55-100% for NH+4-N. The total surface water volume had dilution effects in the upper and middle reaches (3-28%) and condensing effects in the lower reaches (2-37%). Precipitation and vegetation dynamics contributed slightly. The primary unfavorable factors were the growing agricultural pollution discharges and water consumption in the upper and middle reaches that also threatened the lower reaches. This study is expected to provide in-depth insights for the systematic response of regional water quality to combined human interventions and references for water quality management in other arid and semi-arid river basins worldwide.