The Norton Sound area has been home to Yupik and Inupiat for many centuries. It is the boundary between the two peoples; the Inupiat live to the north and the Yup'ik to the south. The town of Nome is along the northern edge of Norton Sound. The villages of Elim, Golovin, Stebbins, White Mountain, Koyuk, Shaktoolik, St. Michael and Unalakleet are on the shores or waterways flowing into Norton Sound. The Iditarod Trail Sled Dog Race runs through coastal villages between Unalakleet and Nome.
The seaplane tender USS Norton Sound was named after the inlet.