Soil organic carbon (SOC) simply cannot be managed if its amounts, changes and locations are not well known. Thus, evaluations of the spatio-temporal dynamics of SOC stock under future climate change are crucial for the adaptive management of regional carbon sequestration. Here, we evaluated the dynamics of SOC stock to a 60 cm depth in the middle Qilian Mountains (1755–5051 m a.s.l.) by combining systematic measurements from 138 sampling sites with a machine learning model. Our results reveal that the combination of systematic measurements with the machine learning model allowed spatially explicit estimates of SOC change to be made. The average SOC stock in the middle Qilian Mountains was expected to decrease under future climate change, while the size and direction of SOC stock changes seemed to be elevation-dependent. Specifically, in comparison with the 2000s, the mean annual precipitation was projected to increase by 18.37, 19.80 and 30.80 mm, and the mean annual temperature was projected to increase by 1.9, 2.4 and 2.9 °C under the Representative Concentration Pathway (RCP) 2.6 (low-emissions pathway), RCP4.5 (low-to-moderate-emissions pathway), and RCP8.5 (high-emissions pathway) scenarios by the 2050s, respectively. Accordingly, the area-weighted SOC stock and total storage for the whole study area were estimated to decrease by 0.43, 0.63 and 1.01 kg m^–2 and 4.55, 6.66 and 10.62 Tg under the RCP2.6, RCP4.5 and RCP8.5 scenarios, respectively. In addition, the mid-elevation zones (3100–3900 m), especially the subalpine shrub-meadow Mollic Leptosols, were projected to experience the most intense carbon loss. However, the higher elevation zones (>3900 m), especially the alpine desert zone, were characterized by significant carbon accumulation. As for the low-elevation zones (<2900 m), SOC was projected to be less varied under future climate change scenarios. Thus, the mid-elevation zones, especially the subalpine shrub-meadows and Mollic Leptosols, should be given priority in terms of reducing CO₂ emissions in the Qilian Mountains.