PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES: The Arctic is experiencing unprecedented rates of sea ice loss in concert with expanding anthropogenic activities that may have compounding effects on marine ecosystems. The Northwest Passage and Northern Sea Route have recently seen the advent of commercial traffic, raising questions of how to juggle economic development and conservation. Here we show the vulnerability of 80 subpopulations of seven endemic Arctic marine mammal species to vessel traffic across the Northwest Passage and Northern Sea Route during the open-water season, accompanied by estimates of uncertainty that highlight additional research needs. As global, national, and local organizations sharpen their focus on the Arctic, our results provide a framework to evaluate environmental impacts to the region’s most iconic and sensitive species.