Previous studies that quantified variations in runoff have mainly focused on the combined impacts of climate and human activities or climate and land cover change. Few have separated land cover change from human activities, which is critical for effective management of water resources. This study aims to investigate the impact of changing environmental conditions on runoff using the Soil and Water Assessment Tool (SWAT) model; we examined three categories: climate, land cover change and direct human activities. The study area was the Wei River Basin, a typical arid to semi-arid basin that was divided into five sub-zones (UZ, MZ, DZ, JZ and BZ). Our results showed the following: (1) the calibrated SWAT model produced satisfactory monthly flow processes over the baseline period from 1978 to 1986; (2) compared to the baseline period, the impact of climatic variations decreased and the impact of direct human activities increased from the 1990s to the 2000s, while the impact of land cover change was generally stable; and (3) climatic variations were the main cause of runoff declines over the entire basin during the 1990s and in the UZ, MZ and JZ areas during the 2000s, while direct human activities were most important in the DZ and BZ areas during the 2000s.