The Fram Strait is one of the largest gateways through which meltwater and sea ice are exported to the subarctic North Atlantic, transiting the North-East Greenland shelf via the southward flowing East Greenland Current. Observations indicate a recent freshening of the East Greenland Current that may have implications for wider oceanic circulation regimes. The North-East Greenland shelf is an opportune region to assess these changes back through time. Paleoceanographic reconstructions from the North-East Greenland shelf are sparse and their temporal coverage is limited to the Holocene, limiting our ability to assess the impact of rapid climatic variations on marine conditions, such as during the Younger Dryas/Holocene transition. Here, we present data from a well-dated marine sediment core retrieved from the North-East Greenland shelf (74°N; east of Young Sound-Tyrolerfjord system) that captures the late Younger Dryas Stadial through to the Mid-Holocene at sub-centennial resolution. We apply a multi-proxy approach to reconstruct changes in productivity, surface and bottom ocean conditions. We show that at 74° N the presence of warm Atlantic waters on the inner North-East Greenland shelf was limited to the late Younger Dryas, as the Greenland Ice Sheet retreated landward and isostatic rebound caused the area to uplift. A unique dimension to this record is its location within one of the few biological hotspots on the East Greenland shelf today; the Sirius Water polynya. Archaeological studies indicate the polynya was forming as early as 4500 years ago, but nothing is known about its evolution from a marine perspective. Cooling of bottom waters, increasing sea-surface productivity and more frequent open water conditions indicate an Early Holocene onset of the Sirius Water (ca. 10–8.7 ka BP).