The Middle Fork is perhaps the best smallmouth bass stream in Illinois, due mainly to its clean water, gravel bottom, and rocky riffles. There are also walleye, Kentucky spotted, and an occasional sauger or northern pike moving in from other areas. Although largemouth bass and big channel catfish are often taken from the river, they are most abundant in the strip mine ponds of Kickapoo State Park. Also in Kickapoo's Clear Pond, IDNR operates a put-and-take trout fishery.

By mid-summer water levels drop and the water becomes clear, so fishermen can switch from live bait to artificial lures. Canoeing becomes less challenging due to the low water, giving access to the entire river to fishing enthusiasts using waders and canoes.