Glaciers are crucial water resources for arid inland rivers in Northwest China. In recent decades, glaciers are largely experiencing shrinkage under the climate-warming scenario, thereby exerting tremendous influences on regional water resources. The primary role of understudying watershed scale glacier changes under changing climatic conditions is to ensure sustainable utilization of regional water resources, to prevent and mitigate glacier-related disasters. This study maps the current (2020) distribution of glacier boundaries across the Kaidu-Kongque river basin, south slope of Tianshan Mountains, and monitors the spatial evolution of glaciers over five time periods from 2000–2020 through thresholded band ratios approach, using 25 Landsat images at 30 m resolution. In addition, this study attempts to understand the role of climate characteristics for variable response of glacier area. The results show that the total area of glaciers was 398.21 km2 in 2020. The glaciers retreated by about 1.17 km2/a (0.26%/a) from 2000 to 2020.The glaciers were reducing at a significantly rapid rate between 2000 and 2005, a slow rate from 2005 to 2015, and an accelerated rate during 2015–2020. The meteorological data shows slight increasing trends of mean annual temperature (0.02°C/a) and annual precipitation (2.07 mm/a). The correlation analysis demonstrates that the role of temperature presents more significant correlation with glacier recession than precipitation. There is a temporal hysteresis in the response of glacier change to climate change. Increasing trend of temperature in summer proves to be the driving force behind the Kaidu-Kongque basin glacier recession during the recent 20 years.