Sisimiut (Greenlandic: [sisimiut]), also known by its Danish name Holsteinsborg, is the capital and largest city of the Qeqqata municipality, the second-largest city in Greenland, and the largest Arctic city in North America. It is located in central-western Greenland, on the coast of Davis Strait, approximately 320 km (200 mi) north of Nuuk.

Sisimiut literally means "the residents at the foxholes" (Danish: Beboerne ved rævehulerne). The site has been inhabited for the last 4,500 years, first by peoples of the Saqqaq culture, then Dorset culture, and then the Thule people, whose Inuit descendants form the majority of the current population. Artifacts from the early settlement era can be found throughout the region, favored in the past for its plentiful fauna, particularly the marine mammals providing subsistence for the early hunting societies. The population of modern Greenlanders in Sisimiut is a mix of the Inuit and Danish peoples, who first settled in the area in the 1720s, under the leadership of the Danish missionary, Hans Egede.

Today, Sisimiut is the largest business centre north of the national capital of Nuuk and is one of the fastest growing cities in Greenland. Fishing is the principal industry in Sisimiut, although the town has a growing industrial base. KNI and its subsidiary Pilersuisoq, a state-owned chain of all-purpose general stores in Greenland, have their base in Sisimiut. Architecturally, Sisimiut is a mix of traditional, single-family houses, and communal housing, with apartment blocks raised in the 1960s during a period of town expansion in Greenland. Sisimiut is still expanding, with the area north of the port, on the shore of the small Kangerluarsunnguaq Bay reserved for a modern suburb-style housing slated for construction in the 2010s. Several professional and general schools are based in Sisimiut, providing education to the inhabitants of the city and to those from smaller settlements in the region. The new Taseralik Culture Centre is the second cultural centre to be established in Greenland, after Katuaq in Nuuk.

The city has its own bus line, and is the northernmost year-round ice-free port in the country, a shipping base for western and northwestern Greenland. Supply ships head from the commercial port towards smaller settlements in more remote regions of Uummannaq Fjord, Upernavik Archipelago, and as far as Qaanaaq in northern Greenland. Sisimiut Airport, the town airport is served by Air Greenland, providing connections to other towns on the western coast of Greenland, and through Kangerlussuaq Airport, to Europe.

Sisimiut has been a settlement site for around 4,500 years, with the people of the Saqqaq culture arriving from Arctic Canada during the first wave of immigration, occupying numerous sites on the coast of western Greenland. At that time, the shoreline was up to several dozen meters above the present line, gradually decreasing in time due to post-glacial rebound. The Saqqaq remained in western Greenland for nearly two millennia. Unlike the following waves of migrants in the millennium following their disappearance, the Saqqaq left behind a substantial number of artifacts, with plentiful archeological finds on the coast of Davis Strait, from Disko Bay (Greenlandic: Qeqertarsuup Tunua) in the north—to the coast of Labrador Sea near Nuuk in the south.

Research has uncovered the changing settlement pattern, exhibiting transition from the single-family dwellings to tiny villages of several families. The types of dwelling varied from tent rings made of the hides of hunted mammals, to stone hearths, with no evidence of communal living in larger structures. In contrast, there is evidence for reindeer hunting as a coordinated effort of either villagers or groups of more loosely related individuals, with gathering places in proximity of the hunting grounds being found. Despite recent advances in DNA research based on hair samples from the ancient Saqqaq migrants (which gives insight into their origin), the reason for the decline and subsequent disappearance of the culture are not yet known.

After several hundred years of no permanent habitation, the second wave of migration arrived from Canada, bringing the Dorset people to western Greenland. The first wave of immigrants, known as Dorset I, arrived around 500 BCE, inhabiting the region for the next 700 years. The early Dorset people were followed later by the Dorset II people; however, no artifacts have been discovered from the later era around Sisimiut, and few artifacts from the era of Dorset I have been uncovered in archaeological sites, with the finds often limited to harpoon heads and numerous animal bones. The largest number of Dorset culture artifacts can be found farther north in the Disko Bay region; there are poorer finds farther to the south, disappearing completely on the coast of Labrador Sea in southwestern Greenland.

The shoreline was still at a higher altitude than today, with the Sisimiut valley east of the Kangerluarsunnguaq Bay, partially under sea. Many Thule artifacts and graves from the several centuries of permanent settlement remain scattered in the region. Rich in fauna, the coastal region from Sisimiut to Kangaamiut was particularly attractive for migrants, and due to a large number of historical artifacts it is currently listed as a candidate for the UNESCO World Heritage Site, with the application received in 2003.