Due to their large mass, ice sheets induce significant stresses in the Earth’s crust. Stress release during deglaciation can trigger large-magnitude earthquakes, as indicated by surface faults in northern Europe. Although glacially-induced stresses have been analyzed in northern Europe, they have not yet been analyzed for Greenland. We know that the Greenland Ice Sheet experienced a large melting period in the early Holocene, and so here, we analyze glacially-induced stresses during deglaciation for Greenland for the first time. Instability occurs in southern Greenland, where we use a combined analysis of past sea level indicators and a model of glacially-triggered fault reactivation to show that deglaciation of the Greenland Ice Sheet may have caused a large magnitude earthquake around 10,600 years ago offshore south-western Greenland. The earthquake may have shifted relative sea level observations by several meters. If the earthquake-induced stress release was created during a single event, it could have produced a tsunami in the North Atlantic Ocean with runup heights of up to 5 m in the British Isles and up to 7.5 m along Canadian coasts.