Glaciological and oceanographic observations coupled with numerical models show that warm Circumpolar Deep Water (CDW) incursions onto the West Antarctic continental shelf cause melting of the undersides of floating ice shelves. Because these ice shelves buttress glaciers feeding into them, their ocean-induced thinning is driving Antarctic ice-sheet retreat today. Here we present a multi-proxy data based reconstruction of variability in CDW inflow to the Amundsen Sea sector, the most vulnerable part of the West Antarctic Ice Sheet, during the Holocene epoch (from 11.7 thousand years ago to the present). The chemical compositions of foraminifer shells and benthic foraminifer assemblages in marine sediments indicate that enhanced CDW upwelling, controlled by the latitudinal position of the Southern Hemisphere westerly winds, forced deglaciation of this sector from at least 10,400 years ago until 7,500 years ago—when an ice-shelf collapse may have caused rapid ice-sheet thinning further upstream—and since the 1940s. These results increase confidence in the predictive capability of current ice-sheet models.