Glacier hypsometry provides a first-order approach for assessing a glacier's response to climate forcings. We couple the Randolph Glacier Inventory to a suite of in situ observations and climate model output to examine potential change for the ∼27,000 glaciers in Alaska and northwest Canada through the end of the 21st century. By 2100, based on Representative Concentration Pathways (RCPs) 4.5–8.5 forcings, summer temperatures are predicted to increase between +2.1 and +4.6°C, while solid precipitation (snow) is predicted to decrease by −6 to −11%, despite a +9 to +21% increase in total precipitation. Snow is predicted to undergo a pronounced decrease in the fall, shifting the start of the accumulation season back by ∼1 month. In response to these forcings, the regional equilibrium line altitude (ELA) may increase by +105 to +225 m by 2100. The mass balance sensitivity to this increase is highly variable, with the most substantive impact for glaciers with either limited elevation ranges (often small (<1 km2) glaciers, which account for 80% of glaciers in the region) or those with top-heavy geometries, like icefields. For more than 20% of glaciers, future ELAs, given RCP 6.0 forcings, will exceed the maximum elevation of the glacier, resulting in their eventual demise, while for others, accumulation area ratios will decrease by >60%. Our results highlight the first-order control of hypsometry on individual glacier response to climate change, and the variability that hypsometry introduces to a regional response to a coherent climate perturbation.