The Missouri portion of the route ran from Kansas City to Quincy by way of Hannibal.
The route also passed through La Belle, Edina, Kirksville, Milan, Harris, Liberty, Excelsior Springs, Richmond, Carrollton, Chillicothe, Trenton and Princeton.
The Cannon Ball Route passes through Bushnell paralleling the CB&Q railroad north to Galesburg and ran largely on what is now U.S. 34 from Galesburg to Chicago, except for diversions to the city centers of Buda, Leland, and Bristol.
The route then passed through downtown Montgomery and Aurora before running east-northeast to Naperville.
Here, the Cannon Ball Route may have followed any of a number of streets before joining the Chicago-Kansas City-Gulf Highway in Maywood for the remainder of the journey into Chicago.