The Inughuit are descendants of the Thule culture people who migrated from Canada to Greenland about A.D. 900. In the mid-1880s several polar expeditions visited Inughuit territory in search of Sir John Franklin, who was missing in his attempt to find the Northwest Passage. In the 1860s a small band of Canadian Eskimo settled in Inughuit territory and taught the Inughuit to build kayaks, to hunt from kayaks, to fish with leisters, and to hunt caribou with bows and arrows. Prior to that time caribou were believed to be poison and were not eaten. With the kayak, food shortages became less of a threat to survival with only one crisis period in late winter before the sun returned. From 1891 to 1909 Robert Peary spent much time among the Inughuit during his quests to reach the North Pole, which he claimed to reach in 1909 accompanied by Matthew Henson and four Inughuit, Odaq, Iggianguaq, Sigdluk, and Ukujaq. Frederick Cook also may have reached the North Pole in April 1908 with two Inughuit, Apilaq and Itukusuk. Among changes brought by Peary were rifles and ammunition for hunting, iron sewing needles and other Western tools, coffee, tea, sugar, and other processed foods.

Following his 1903-1904 visit, Knud Rasmussen became the protector of the Inughuit, introducing Christianity and establishing a Lutheran mission in 1909. Baptisms for adults were actively conducted from 1912 to 1934. To ensure the regular flow of European goods, Rasmussen had a store built at Uummannaq in 1910 with Peter Freuchen serving as the first storekeeper until 1920. In 1927 Rasmussen established the Hunter's Council with the non-Inughuit storekeeper, minister, and physician and three of the best Inughuit hunters as members. The council established the Thule Law in 1929 which regulated hunting, settled conflicts, and provided assistance to the poor. The Thule Law lasted until 1963 when the West Greenland municipal system became the central authority.

In 1930 Uummannaq housed a government center, a new store, a church, a hospital, a school, and homes for the minister and physician. In 1937 Inughuit territory was incorporated into the Danish Greenland colony, with the Inughuit, like other Greenlanders, becoming Danish citizens in 1953. Between 1951 and 1955 the United States built Thule Air Base near Uummannaq. Pollution from the base made hunting poor and the village population had to move to Qaanaaq in 1953. In 1968 a B-52 bomber with four atomic bombs crashed, leaving ground radiation that restricted hunting in the area. In May 1979 the Inughuit along with other Greenlanders were given home rule, with only defense and foreign relations matters resting with Denmark. In the 1980s the Inughuit joined other members of the Inuit Circumpolar Conference to fight against the Canadian Arctic Pilot Project (APP) , fearing that their hunting grounds would be destroyed by year-round oil-tanker traffic. The APP was eventually discontinued.