The Heihe River drainage basin is one of the endangered ecological regions of China. The shortage of water resources is the bottleneck, which constrains the sustainable development of the region. Many scholars in China have done researches concerning this problem. Based on previous researches, this paper analyzed characteristics, tendencies, and causes of annual runoff variations in the Yingluo Gorge (1944–2005) and the Zhengyi Gorge (1954–2005), which are the boundaries of the upper reaches, the middle reaches, and the lower reaches of the Heihe River drainage basin, by wavelet analysis, wavelet neural network model, and GIS spatial analysis. The results show that: (1) annual runoff variations of the Yingluo Gorge have principal periods of 7 years and 25 years, and its increasing rate is 1.04 m³/s·10y; (2) annual runoff variations of the Zhengyi Gorge have principal periods of 6 years and 27 years, and its decreasing rate is 2.25 m³/s·10y; (3) prediction results show that: during 2006–2015, annual runoff variations of the Yingluo and Zhengyi gorges have ascending tendencies, and the increasing rates are respectively 2.04 m³/s·10y and 1.61 m³/s·10y; (4) the increase of annual runoff in the Yingluo Gorge has causal relationship with increased temperature and precipitation in the upper reaches, and the decrease of annual runoff in the Zhengyi Gorge in the past decades was mainly caused by the increased human consumption of water resources in the middle researches. The study results will provide scientific basis for making rational use and allocation schemes of water resources in the Heihe River drainage basin.