The recorded runoff of the major rivers in China has been changing due to environment change. It is of significance to quantitatively analyze attribution of runoff change for supporting water resources assessment and management in many practices. Based on abrupt change detection of annual runoff series from 1956—2018 measured at the 8 representative hydrometric stations on major rivers in China, impacts of climate change and human activities on runoff changes were investigated by using hydrological simulation approach. Results show that (1) The abrupt change of annual runoff series recorded at the Wujiadu station on the Huai River, Datong station on the Yangtze River and the Wuzhou staion on the Pearl River are not detectable. However, the abrupt changes have been found for the recorded annual runoff series of the major rivers in North China with the earliest and the latest abrupt change years occurring in 1965 for the Tieling station on the Liao River and in 2003 for the Haerbin station on the Songhua River, respectively. The relationships between runoff and precipitation for periods before and after abrupt change year were markedly changed probably due to human activities. (2) RCCC-WBM model not only performs well on monthly runoff simulation for humid South China, but also achieves good simulation result for major rivers in arid North China. The model has been proved being qualified to naturalize runoff in the human-disturbed periods for major rivers in China. (3) In general, human-induced runoff changes are higher than the climatic impacts for major rivers in the North China, while climate change is a dominant driver of runoff variation for the Hai River and major rivers of China in its south.