Based on landuse maps and soil distribution maps of three years (1985, 1995, and 2005) and basic information, such as temperature, precipitation, and runoff, from the main hydrological stations in the Zhangweinan River Basin during the period from 1960 to 2010, this paper establishes a distributed hydrological model, soil and water assessment tool (SWAT) model, and proposes an itemized quantitative method to measure the impact of climate changes and human activities on runoff. By simulating different scenarios, the contribution rates of different humanactivity driving factors, such as water and soil conservation, urbanization, hydraulic engineering, and social economy water consumption, to runoff in different eras were quantitatively calculated based on the quantitative analysis of the impact of climate changes and human activities on runoff in the Zhangweinan River Basin. The results show that there are different impact degrees of climate changes and human activities on runoff in different eras. Compared with the baseline period from 1960 to 1978, the contribution rates of climate changes and human activities to runoff of the changing period from 1979 to 2010 are 29.39％ and 70.61％, respectively. All driving factors of human activities caused runoff to decrease, except for urbanization. The impact of social economy water consumption is greatest, accounting for more than 50％ of the total runoff reduction caused by human activities.