IL 110 was created through legislation on May 27, 2010, as the designated route for the Illinois portion of the Chicago–Kansas City Expressway.

The Expressway starts in downtown Claycomo on I-35 and leaves the city in a northeast direction.

[4] IL 110 crosses into Illinois from the Mark Twain Memorial Bridge east of Hannibal.

There is a two-mile (3.2 km) stretch of the route in Good Hope, where it is reduced from a four-lane divided highway to a three-lane undivided street with a center turn lane.

The Cannon Ball Route was a historic auto trail that ran from Hannibal, Missouri east-northeast to Chicago, Illinois.

Efforts to construct a direct route from Chicago to Kansas City have been in the planning stages since its exclusion from the Interstate Highway System in the 1950s.

[6][7] The proposed highway took different forms over time: a 1989 study found that a full, limited-access tollway running from Kansas Turnpike at Kansas City to the Indiana Toll Road at Gary or Tri-State Tollway near the Joliet area would cost $2–$2.5 billion, if funded entirely by private investors.