Indigenous peoples were the first settlers around the lake after the retreat of glacial ice. Along the south shore, east of Hay River is the abandoned Pine Point Mine and the company town of Pine Point. The only community in the East Arm is Łutselk'e, a hamlet of about 350 people, largely Chipewyan Indigenous peoples of the Dene Nation, and the abandoned winter camp and Hudson's Bay Company post Fort Reliance.

Towns situated on the lake include (clockwise from east) Łutselk'e, Fort Resolution, Hay River, Hay River Reserve, Behchokǫ̀, Yellowknife, Ndilǫ, and Dettah. The lake shares its name with the First Nations peoples of the Dene family called Slavey by their enemies the Cree. Its given volume ranges from 1,070 km 3 (260 cu mi) to 1,580 km 3 (380 cu mi) and up to 2,088 km 3 (501 cu mi) making it the 10th or 12th largest by volume. It covers an area of 27,200 km 2 (10,500 sq mi) in the southern part of the territory. Great Slave Lake ( French: Grand lac des Esclaves ), known traditionally as Tıdeè in Tłı̨chǫ Yatıì (Dogrib), Tinde’e in Wıìlıìdeh Yatii / Tetsǫ́t’ıné Yatıé (Dogrib / Chipewyan), Tu Nedhé in Dëne Sųłıné Yatıé (Chipewyan), and Tucho in Dehcho Dene Zhatıé (Slavey), is the second-largest lake in the Northwest Territories of Canada (after Great Bear Lake), the deepest lake in North America at 614 m (2,014 ft), and the tenth-largest lake in the world by area. Yellowknife, Hay River, Behchokǫ̀, Fort Resolution, Łutselk'e, Hay River Reserve, Dettah, Ndilǫġ Shore length is not a well-defined measure. Hay River, Slave River, Taltson River, Lockhart River, Yellowknife River, Snare River (through Marian Lake and Frank Channel), Marian River (through Marian Lake and Frank Channel), Stark River

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