Glacier meltwater change in the north‐eastern edge of the Tibetan Plateau is greatly important for the projection of the impact of future climate change on local water resource management. Although the glaciated area is only approximately 4% of the Upper Reach of the Shule River Basin (URSRB), the average glacier meltwater contribution to river run‐off was approximately 23.6% during the periods 1971/1972 to 2012/2013. A new glacier melting module coupled with the macroscale hydrologic Variable Infiltration Capacity model (VIC‐CAS) was adopted to simulate and project changes in the glacier meltwater and river run‐off of the URSRB forced by downscaled output of the BCC‐CSM1.1(m), CANESM2, GFDL‐CM3, and IPSL‐CM5A‐MR models. Comparisons between the observed and simulated river run‐offs and glacier area changes during the periods 2000/2001, 2004/2006, 2008/2009, and 2012/2013 suggest that the simulation is reasonable. Due to increases in precipitation, the annual total run‐off is projected to increase by approximately 2.58–2.73 × 108 m3 in the 2050s and 0.28–1.87 × 108 m3 in the 2100s compared with run‐off in the 2010s based on the RCP2.6 (low greenhouse gas emission) and RCP4.5 (moderate greenhouse gas emission) scenarios, respectively. The contribution of glacier meltwater to river run‐off will more likely decrease to approximately 10% and less than 5% during the 2050s and 2100s, respectively.