Quantifying the contributions of climate change and human activities on runoff changes is of great importance for water resource management, sustainable water resource utilization, and sustainable development of society. In this study, hydrological and climatic data from hydrological and meteorological stations in the headwaters of the Yangtze River (YRHA) from 1966 to 2013 were used to quantitatively attribute the runoff change to the impacts of climate change and human activities separately. Firstly, the change trends in precipitation, runoff depth and potential evapotranspiration were analyzed by the Mann-Kendall test method. Three methods, secondly, including ordered clustering, Mann-Kendall and cumulative anomaly curve were adopted to detect the change points of runoff at Zhimenda hydrological station and partition the whole study period into two sub-periods at the change point (base and impacted periods). Then, the elasticity coefficient method based on the Budyko hypothesis was applied to calculate elasticity coefficients of runoff to precipitation, potential evapotranspiration and land use/cover during the two periods, and to evaluate the contributions of climate change and human activities. Results indicated that during 1966–2013, runoff depth, precipitation and potential evapotranspiration all showed a significant increasing trend, with increasing rates of 7.26 mm decade−1, 18.725 mm decade−1 and 7.228 mm decade−1, respectively. One change point (2004) was detected for the annual runoff, and 1966–2003 and 2004–2013 were respectively identified as base and impacted periods. The results of elasticity coefficients showed that the runoff depth was most sensitive to the change of precipitation during the two periods. The relative contributions of precipitation, potential evapotranspiration and parameter n to runoff changes were 99.7%, −6.08% and 3.88%, respectively. Furthermore, the coupled contribution rate of other factors was less than 2.5%. Generally, results indicated that precipitation is the main factor on the historical runoff changes in this basin.