Abstract: There is a growing concern over the allocation of water resources in Central Asia under the background of climate change. Therefore, it is of great significance to study the hydrological changes of the trans-boundary rivers in Central Asia for the upstream and downstream countries to rationally make use of the water resources. The stream flow and its response to climate factors are shown in this paper, based on instrumental data from 1936 to 2015 in the Chu River Basin. The results show that: ① During those 80 years, a warming-wetting trend occurred in the Chu River Basin, and the stream flow in the plain area showed a significant inter-decadal fluctuation and was concentrated in winter and spring. ② Wavelet analysis showed a 26-year first main cycle and a 12-year second main cycle during those 80 years. ③ Temperature abrupt changes occurred in 1987, and the runoff abrupt changes occurred in 2001. ④ The annual stream flow was significantly positively correlated with the June-May precipitation(r = 0.61, P < 0.01), and correlation between the annual stream flow and the April-July temperature was relatively low(r = −0.37, P < 0.01). However, the correlation between April-July temperature and annual runoff increased under warming conditions, therefore, the increase of evaporation caused by climate warming may be an important reason for the decrease of stream flow in the plain area of the lower reaches of the Chu River.