The Little Ice Age may have reduced the population of the Great Auk by exposing more of their breeding islands to predation by Polar Bears, but massive exploitation for their down drastically reduced the population. By the mid-16th century, the nesting colonies along the European side of the Atlantic were nearly all eliminated by humans killing this bird for its down, which was used to make pillows. In 1553, the auk received its first official protection, and in 1794 Great Britain banned the killing of this species for its feathers. In St. John's, individuals violating a 1775 law banning hunting the Great Auk for its feathers or eggs were publicly flogged, though hunting for use as fishing bait was still permitted.

On the North American side, eider down was initially preferred, but once the eiders were nearly driven to extinction in the 1770s, down collectors switched to the auk at the same time that hunting for food, fishing bait, and oil decreased.

With its increasing rarity, specimens of the Great Auk and its eggs became collectible and highly prized by rich Europeans, and the loss of a large number of its eggs to collection contributed to the demise of the species. Eggers, individuals who visited the nesting sites of the Great Auk to collect their eggs, quickly realized that the birds did not all lay their eggs on the same day, so they could make return visits to the same breeding colony. Eggers only collected eggs without embryos growing inside of them and typically discarded the eggs with embryos.

It was on the islet of Stac an Armin, St Kilda, Scotland, in July 1844, that the last Great Auk seen in the British Isles was caught and killed. Three men from St Kilda caught a single "garefowl", noticing its little wings and the large white spot on its head. They tied it up and kept it alive for three days, until a large storm arose. Believing that the auk was a witch and the cause of the storm, they then killed it by beating it with a stick. It is the only British bird made extinct in historic times.

The last colony of Great Auks lived on Geirfuglasker (the "Great Auk Rock") off Iceland. This islet was a volcanic rock surrounded by cliffs which made it inaccessible to humans, but in 1830 the islet submerged after a volcanic eruption, and the birds moved to the nearby island of Eldey, which was accessible from a single side. When the colony was initially discovered in 1835, nearly fifty birds were present. Museums, desiring the skins of the auk for preservation and display, quickly began collecting birds from the colony. The last pair, found incubating an egg, was killed there on 3 July 1844, on request from a merchant who wanted specimens, with Jón Brandsson and Sigurður Ísleifsson strangling the adults and Ketill Ketilsson smashing the egg with his boot.

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