The need for better understanding of long-term climate and environmental variability in the Foxe Basin (Nunavut, Canada) is highlighted by the major environmental changes in this highly sensitive region, which occupies a transitional position between areas undergoing drastic and more subtle changes in the High and Low Canadian Arctic over the course of the last millennium, respectively. However, high-resolution long-term climate records remain scarce in the Foxe Basin region even though it is of key importance to understanding Holocene climate evolution since the last deglaciation. In order to reconstruct the regional postglacial climatic and environmental variability, we adopted a multi-proxy paleolimnological approach analysing sedimentary records retrieved from Nettilling Lake on southern Baffin Island, involving elemental geochemistry from high-resolution µ-XRF analyses, diatom assemblage composition and oxygen isotope records from fossil diatom silica (δ18Odiatom). The oxygen isotope composition of diatoms (δ18Odiatom) yields extremely large δ18Odiatom variations in the core of more than 13‰ which are mainly driven by changes in the isotopic composition of the lake water due to a shift from glacio-marine to brackish (at ca. 7400 yr cal BP) towards lacustrine conditions (at ca. 6000 yr cal BP) associated with decreasing salinity also documented by shifts in the composition of diatom assemblages. Our study provides evidence that paleo-salinity can be inferred from δ18Odiatom. Additionally, in the lacustrine section of the core,, δ18Odiatom may also serve as a proxy for past air temperatures recording a late Holocene cooling of about 4°C for the greater Baffin region. Furthermore, the results obtained from our study provide new insights into the timing of regional glacier retreat (ca. 8300 cal BP) and the duration of the postglacial marine invasion (from ca. 7400 cal BP to ca. 6000 cal. BP), thereby complementing ongoing research of postglacial environmental dynamics in the Foxe Basin and on south-western Baffin Island.