The richness of the Atlantic Ocean lured Europeans to the ecozone's waters in the 16th century and there is evidence of Norse and Spanish fishing settlements in the preceding centuries. Legendary quantities of fish were scooped out of the waters off the east coast. It became an accepted and lucrative notion that there were more fish in the sea than could ever be harvested. The sea provided a sometimes meagre living for fishing families, while enriching merchants and financiers. But by the 1990s, national and international fishing fleets had nearly wiped out Canada's cod stocks. A way of life that supported the people of eastern Canada for 400 years was in jeopardy. In 1992, the government of Canada imposed a moratorium on cod fishing in most Atlantic Canadian waters in hopes the stocks would rebuild.

The northern reaches of the ecozone are sparsely populated. Small towns and villages dot the Newfoundland and Labrador coasts and Baffin Island. Human activities include seal hunting, subsistence fishing, resource exploration and burgeoning tourism. But large offshore trawlers still take their official quotas — sometimes more — of any commercially valuable fish they can find. Concern is now emerging about the imminent exploitation of giant mineral deposits recently found at Voisey's Bay on the northern Labrador coast. Some wonder how the mines will avoid polluting the streams and rivers that run to the ocean.

Population density increases dramatically further south along the shores of the Gulf of St. Lawrence, which suffer from the effects of industrial and municipal sewage. Endangered marine mammals, such as the Beluga Whale, are sensitive to toxins in the water. Urban sprawl along the banks of the St. Lawrence River and around coastal cities has destroyed much wildlife habitat. Municipal garbage dumps have encouraged gull populations to rise, forcing out other species.