Although geological and modelling evidence indicate that the last glacial inception in North America was in NE Canada, little is known about the glacial response of the nearby western Greenland Ice Sheet (GIS) during the glacial advance of marine oxygen isotope stage 4 (MIS4). Our multi-proxy study of a marine sediment core collected about 60 km southwest of the Outer Hellefisk Moraines demonstrates that in the southern Davis Strait region the most extreme Greenland shelf glaciation of the last glacial cycle occurred during MIS 4, with another prominent glacial advance at 37–33 kyr BP. During those periods the GIS likely reached the Outer Hellefisk Moraines in this area. Except for these two periods, our data suggest significant advection of relatively warm Irminger Sea Water by the West Greenland Current since MIS 4. This advection likely limited the extent of the MIS2 glaciation on the SW Greenland shelf. Decreased precipitation over southwestern Greenland predicted by atmospheric models as a downstream effect of a much larger MIS2 Laurentide Ice Sheet may have played an additional role.