Along the southern border of Illinois, there is a 133 mile stretch of the Ohio River running from the confluence with the Wabash River near Uniontown, Kentucky, in the east to the confluence with the Mississippi River near Fort Defiance in the west. There are good fisheries in the open river stretches and pool areas, especially the Smithland Pool near the high lift dam near Smithland, Kentucky. There is good tailwater fishing at Smithland Dam. There are good boat ramps at: Old Shawneetown, Cave in Rock, Tower Rock, Elizabethtown, Rosiclare, Golconda Marina, Golconda and Barren Creek. Good fishing can also be found on the Illinois side near one for the many small creek confluences, such as Lusk Creek, Barren Creek, Big Creek, Big Grand Pierre Creek, Bay Creek, Dog Creek, Alcorn Creek and the Saline River.
Overall, Ohio River is the 7th most popular fly fishing river of all 8 fly fishing spots in Illinois.