Nettilling Lake (Baffin Island, Nunavut) is currently the largest lake in the Canadian Arctic Archipelago. Despite its enormous size, this freshwater system remains little studied until the present-day. Existing records from southern Baffin Island indicate that in the early postglacial period, the region was submerged by the postglacial Tyrell Sea due to isostatic depression previously exerted by the Laurentide Ice Sheet. However, these records are temporally and spatially discontinuous, relying on qualitative extrapolation. This paper presents the first quantitative reconstruction of the postglacial environmental succession of the Nettilling Lake basin based on a 8300 yr-long high resolution sedimentary record. Our multi-proxy investigation of the glacio-isostatic uplift and subsequent changes in paleosalinity and sediment sources is based on analyses of sediment fabric, elemental geochemistry (m-XRF), diatom assemblage composition, as well as on the first diatom-based oxygen isotope record from the eastern Canadian Arctic. Results indicate that the Nettilling Lake basin experienced a relatively rapid and uniform marine invasion in the early Holocene, followed by progressive freshening until about 6000 yr BP when limnological conditions similar to those of today were established. Our findings present evidence for deglacial processes in the Foxe Basin that were initiated at least 400yrs earlier than previously thought.