Understanding the mechanisms of river runoff variation is important for the effective management of water resources in arid and semi-arid regions. This study uses long-term observational data as a basis for examining the effects of human activities and climate change on the runoff variation of Jinghe River Basin, a typical arid inland basin in northwest China. A distributed hydrological model called the Soil and Water Assessment Tool, combined with a sequential cluster method and a separation approach, was used to quantify and distinguish the effects of human activities and climate change on runoff. The hydrological sequence before 1981 can be considered natural. However, human activities have significantly affected runoff since 1981. The runoff reduction caused by human activities between 1981 and 2008 accounted for 85.7% of the total reduction in the downstream of Jinghe River, whereas that caused by climatic variation was only 14.3%. This observation suggests that human activities are the major driver of runoff variation in the basin. Although the role of climate change in driving runoff variation has been identified to be prevalent and dominant in arid regions, this study highlights the importance of human activities. Copyright © 2013 John Wiley & Sons, Ltd.