The impact of climate change on glaciers and the hydrological processes in the easternmost end of the eastern Tianshan Mountains has yet to be understood. This study investigated the glacier change (area, surface elevation and volume change) and analyzed the variation of the observed runoff series over the past four decades in the Yushugou Basin, Eastern Tianshan Mountains. The hydrological processes were also simulated through the HBV-light model to quantify the impact of climate change on the glacier and runoff. The results showed that the glacier area has decreased by 13% and the total volume has decreased by 0.018 km³ over the past four decades. A significant increasing trend (p < 0.01) was detected for the annual runoff and monthly runoff (May to September; p < 0.01). The simulation results revealed that the Yushugou River was highly recharged by glacial runoff and a negative tendency was found for the glacier mass balance on the basin scale over the past 38 years. As a region with an extremely dry climate and the lowest precipitation in the Tianshan Mountains, the observation and simulation of glaciers is critical to the security assessment of local water resources.