Central Asia, which is one of the most complex regions in the world, is crisscrossed with transboundary rivers shared by several countries. This paper analyzes the effects of climate change and human activities on hydrological processes and water resources in these transboundary rivers over the past half century. The results show that the average temperature in the Tienshan Mountains experienced “sharp” increases in 1998, with the average temperature after 1998 being 1.0°C higher than that during 1960–1998. This rapid warming has accelerated glacier shrinkage and decreases in snow cover. These changes influenced the hydrological processes, causing an earlier runoff peak and aggravated extreme hydrological events. Changes in mountainous hydrological processes affected regional water availability and intensified future water crisis in Central Asia. The mismatched spatial distributions of water and land resources, along with the intense human activities (e.g., overexploitation of water resources), have ultimately led to the present water crisis in Central Asia's river basins. This is the main reason for ongoing water conflicts in the region's transboundary rivers and the ecological disaster of the Aral Sea.