Greenland Ice Sheet mass loss is impacting connected terrestrial and marine hydrologic systems with global consequences. Groundwater is a key component of water cycling in the Arctic, underlying the 1.7e6 km2 ice sheet and forming offshore freshwater reserves. However, despite its vast extent, the response of Greenland’s groundwater to ongoing ice sheet change is unknown. Here we present in-situ observations of deep groundwater conditions under the Greenland Ice Sheet, obtained in a 651-metre-long proglacial bedrock borehole angled under the ice sheet margin. We find that Greenland’s groundwater system responds rapidly and sensitively to relatively minor ice sheet forcing. Hydraulic head clearly varies over multi-annual, seasonal and diurnal timescales, which we interpret as a response to fluid pressure forcing at the ice/bed interface associated with changes in overlying ice loading and ice sheet hydrology. We find a systematic decline in hydraulic head over the eight-year observational period is linked primarily to ice sheet mass loss. Ongoing and future ice thinning will probably reduce groundwater discharge rates, with potential impacts to submarine freshwater discharge, freshwater delivery to fjords and biogeochemical fluxes in the Arctic.