The watershed is bordered to the north by middle Precambrian ores of the Mesabi Iron Range. Underlying the St. Louis itself are mid-Precambrian argillite and graywacke. In its middle reaches the St. Louis flows across silts and clays that once formed the nearly level bed of glacial Lake Upham. Fish and wildlife - Walleye and northern pike are the principle game fish, though smallmouth bass are common from the mouth of the Whiteface River to Cloquet, and channel catfish from Floodwood to Brookston. Timber wolves, bobcats, lynx, beavers, otters, bald eagles and osprey are occasionally sighted.
Big game includes moose, black bears and white-tailed deer.
Probably the first white man to explore this area was Daniel Greysolon, Sieur du Lhut, who traveled here in 1679 and for whom Duluth later was named. The St. Louis River linked Lake Superior with trading posts on the Mississippi River and Vermilion Lake. White settlement of the area began with the La Pointe Treaty of 1854. Increasing settlement and the construction of the Northern Pacific Railroad westward to the Red River valley required huge quantities of timber, much of which was cut in the St. Louis River valley. Iron mining on the Vermilion and Mesabi ranges further increased the demand for lumber and rail transportation.