Outputs from the regional climate model Modèle Atmosphérique Régionale at a spatial resolution of 25 km are used to study 21st century projected surface mass balance (SMB) over six major drainage basins of the Greenland ice sheet (GrIS). The regional model is forced with the outputs of three different Earth System Models (CanESM2, NorESM1 and MIROC5) obtained when considering two greenhouse gas future scenarios with levels of CO2 equivalent of, respectively, 850 and >1370 ppm by 2100. Results indicate that the increase in runoff due to warming will exceed the increased precipitation deriving from the increase in evaporation for all basins, with the amount of net loss of mass at the surface varying spatially. Basins along the southwest and north coast are projected to have the highest sensitivity of SMB to increasing temperatures. For these basins, the global temperature anomaly corresponding to a decrease of the SMB below the 1980–99 average (when the ice sheet was near the equilibrium) ranges between +0.60 and +2.16 °C. For the basins along the northwest and northeast, these values range between +1.50 and +3.40 °C. Our results are conservative as they do not account for ice dynamics and changes in the ice sheet topography.