Water resources are of vital importance to the development of human society. Mastering the rule of river runoff changes is the basis for achieving sustainable use of water resources. The current research on runoff changes involves three aspects, namely, the interannual change of runoff, the annual distribution characteristics of runoff, and the attribution analysis of runoff changes. Based on the monthly runoff data of Shengzhou Station (SZ), Huangze Station (HZ) and Huashan Station (HS) from 1980 to 2018, the runoff changes in the middle and upper reaches of the Cao’e River are investigated using a variety of research methods. The results show that the annual average runoff showed a downward trend, which changed the greatest at HZ, followed by HS and SZ. The average runoff of all three stations also changed seasonally, which showed a significant downward trend in spring, but that of HZ showed a significant upward trend in winter. Both SZ and HS experienced an abrupt change in annual average runoff in 2003, whereas HZ had no obvious abrupt change. The distribution process curve of runoff in different periods showed a pattern of “three peaks”with the characteristics of “low-high-low”, which happened in March to April, June and August to September, respectively. For SZ and HS, human activities were the main reason for the reduction of runoff during the change period, whereas the reduction of rainfall was responsible for that for HS.