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Palynological, geochemical, and physical records were used to document Holocene paleoceanographic changes in marine sediment core from Dease Strait in the western part of the main axis of the Northwest Passage (core 2005-804-006 PC latitude 68°59.552'N, longitude 106°34.413'W). Quantitative estimates of past sea surface conditions were inferred from the modern analog technique applied to dinoflagellate cyst assemblages. The chronology of core 2005-804-006 PC is based on a combined use of the paleomagnetic secular variation records and the CALS7K.2 time-varying spherical harmonic model of the geomagnetic field. The age-depth model indicates that the core spans the last ~7700 cal years B.P., with a sedimentation rate of 61 cm/ka. The reconstructed sea surface parameters were compared with those from Barrow Strait and Lancaster Sound (cores 2005-804-004 PC and 2004-804-009 PC, respectively), which allowed us to draw a millennial-scale Holocene sea ice history along the main axis of the Northwest Passage (MANWP). Overall, our data are in good agreement with previous studies based on bowhead whale remains. However, dinoflagellate sea surface based reconstructions suggest several new features. The presence of dinoflagellate cysts in the three cores for most of the Holocene indicates that the MANWP was partially ice-free over the last 10,000 years. This suggests that the recent warming observed in the MANWP could be part of the natural climate variability at the millennial time scale, whereas anthropogenic forcing could have accelerated the warming over the past decades. We associate Holocene climate variability in the MANWP with a large-scale atmospheric pattern, such as the Arctic Oscillation, which may have operated since the early Holocene. In addition to a large-scale pattern, more local conditions such as coastal current, tidal effects, or ice cap proximity may have played a role on the regional sea ice cover. These findings highlight the need to further develop regional investigations in the Arctic to provide realistic boundary conditions for climatic simulations.