Understanding and quantifying changes in hydrological systems due to human interference are critical for the implementation of adaptive management of global water resources in the changing environment. To explore the implications of hydrological variations for water resources management, the Wuding River Basin (WRB) in the Loess Plateau, China, was selected as a case study. Based on the Budyko-type equation with a time-varying parameter n, a human-induced waterenergy balance (HWEB) model was proposed to investigate the hydrological variability in the WRB. The investigation showed that runoff continuously reduced by 0.424 mm/a during 19752010, with weakly reducing precipitation and increasing groundwater exploitation causing a decrease in groundwater storage at a rate of 1.07 mm/a, and actual evapotranspiration accounting for more than 90% of precipitation having an insignificantly decreasing trend with a rate of 0.53 mm/a under climate change (decrease) and human impact (increase). Attribution analysis indicated that human-induced underlying surface condition change played a dominant role in runoff reduction by driving an increase in actual evapotranspiration, and that mainly impacted the overall decrease in runoff compounded by climate change during the entire period. It is suggested that reducing the watershed evapotranspiration and controlling groundwater exploitation should receive greater attention in future basin management.