The National Route reenters Illinois on the Mark Twain Memorial Bridge (I-72) from Hannibal, Missouri and follows I-172 north to the IL 57 interchange, where the unbannered route from Chester ends. It follows extant IL 57 into Quincy and then US 24 and IL 96 to a point east of Warsaw, turning west onto that city's Main Street and leaving to the northeast on 6th Street. A short jog east on US 136 in Hamilton returns the Great River Road to IL 96, which it follows, mostly right along the river, through Nauvoo to Niota. The National Route turns northwest there on IL 9 to the Fort Madison Bridge into Fort Madison, Iowa.