Alpine glacier meltwater from the Qilian Mountains (QMs), northeast Tibetan Plateau, is main source of water for the surrounding arid zones. Accurately reconstructing long-term mountain glacier mass balance (MB) and prejecting glacier changes under climate warming are pivotal in cryospheric scientific research. In this study, Laohugou Glacier No. 12 (LHG12), in the western QMs, was selected as a study area. Based on the evaluated and corrected CMIP6 model data, the degree-day and glacier retreat model were used to predict the glacier changes under three scenarios for 2020–2100. The results showed that 1) from 2020–2100, the annual mass loss of LHG12 simulated using CanESM5 and EC-Earth3 increased compared to the measured data in the historical period (2010–2014) (i.e., annual MB of -0.26 m w.e) by a factor of 1.04 and 1.73 under SSP1-2.6, 4.62 and 4.88 under SSP3-7.0, and 6.23 and 7.15 times under SSP5-8.5. 2) By 2100, the ice volume of LHG12 simulated using CanESM5 and EC-Earth3 reduced to 1.00×109 (58.2%) and 1.27×109 (74.0%) m3 under SSP1-2.6, 0.18×109 (10.2%) and 0.15×109 (8.9%) m3 under SSP3-7.0, and 0.03×109 (1.6 %) and 0.01×109 (0.4%) m3 under SSP5-8.5, respectively. 3) Under SSP5-8.5, the LHG12 area simulated using CanESM5 and EC-Earth3 was only 1.87 and 0.75 km2 by 2100. This study lays a foundation for predicting the peak and inflection points of runoff change in the QMs.