Considerable uncertainty surrounds the extent and timing of the advance and retreat of the Greenland Ice Sheet (GIS) on the continental shelf bordering Baffin Bay during the last glacial cycle. Here we use marine geophysical and geological data to show that fast-flowing ice sheet outlets, including the ancestral Jakobshavn Isbræ, expanded several hundred kilometers to the shelf edge during the last glaciation ca. 20 ka. Retreat of these outlets was asynchronous. Initial retreat from the shelf edge was underway by 14,880 calibrated (cal) yr B.P. in Uummannaq trough. Radiocarbon dates from the adjacent Disko trough and adjoining trough-mouth fan imply later deglaciation of Jakobshavn Isbræ, and, significantly, an extensive readvance and rapid retreat of this outlet during the Younger Dryas stadial (YD). This is notable because it is the first evidence of a major advance of the GIS during the YD on the West Greenland shelf, although the short duration suggests that it may have been out of phase with YD temperatures.