Four sediment cores from the central and northern Greenland Sea basin, a crucial area for the renewal of North Atlantic deep water, were analyzed for planktic foraminiferal fauna, planktic and benthic stable oxygen and carbon isotopes as well as ice-rafted debris to reconstruct the environmental variability in the last 23 kyr. During the Last Glacial Maximum, the Greenland Sea was dominated by cold and sea-ice bearing surface water masses. Meltwater discharges from the surrounding ice sheets affected the area during the deglaciation, influencing the water mass circulation. During the Younger Dryas interval the last major freshwater event occurred in the region. The onset of the Holocene interglacial was marked by an increase in the advection of Atlantic Water and a rise in sea surface temperatures (SST). Although the thermal maximum was not reached simultaneously across the basin, benthic isotope data indicate that the rate of overturning circulation reached a maximum in the central Greenland Sea around 7 ka. After 6–5 ka a SST cooling and increasing sea-ice cover is noted. Conditions during this so-called "Neoglacial" cooling, however, changed after 3 ka, probably due to enhanced sea-ice expansion, which limited the deep convection. As a result, a well stratified upper water column amplified the warming of the subsurface waters in the central Greenland Sea, which were fed by increased inflow of Atlantic Water from the eastern Nordic Seas. Our data reveal that the Holocene oceanographic conditions in the Greenland Sea did not develop uniformly. These variations were a response to a complex interplay between the Atlantic and Polar water masses, the rate of sea-ice formation and melting and its effect on vertical convection intensity during times of Northern Hemisphere insolation changes.