Climate change and human activity are two linked factors that alter the spatiotemporal distribution of the available water. Assessing the relative contribution of the two factors on runoff changes can help the planners and managers to better formulate strategies and policies regarding regional water resources. In this work, using two typical sub-basins of the Yellow River as the study area, we first detected the trend and the breakpoint in the annual streamflow data with the Pettitt test during the period 1964–2011. Next, a Budyko-based climate elasticity model and a monthly hydrological model were employed as an integrated method to distinguish the relative contributions of climate change and human activities to the long-term changes in runoff. The results showed that a significant decline in the annual runoff occurred in the two sub-basins during the study period, and the abrupt change point in the annual runoff at the two sub-basins both occurred in 1997. The conceptual hydrological model performed well in reproducing monthly runoff time series at the two sub-basins. The Nash-Sutcliffe efficiency (NSE) between observed and simulated runoff during the validation period exceeds 0.83 for the two sub-basins. Climate elasticity method and hydrological model give consistent attribution results: human activities are the major drivers responsible for the decreased annual runoff in the Ten Great Gullies Basin. The relative contributions of climate change and human activities to the changes in the annual runoff were 22–32% and 68–78%, respectively.