The highway and surrounding region has a long association with gold mining. It was built to service the Circle Mining District, which was very productive in the 1890s, before the discovery of gold in the Klondike. Both historic sites, such as Felix Pedro's 1902 gold discovery which resulted in the founding of Fairbanks, and the preserved gold camp at Chatanika, and active dredging operations line the road.
Much of the highway passes through rugged unpopulated areas.
The Steese Highway is numbered Alaska Route 6 for most of its length, except for the first 11 miles (17 km) from Fairbanks to Fox, which are numbered Alaska Route 2. The highway has been designated as a National Scenic Byway.