Kirksville is the major trade center of northern Missouri, as well as the home of Truman State University. It's also a junction point for two major cross-state routes, US 63 and Missouri 6. These highways, along with Missouri 11, run concurrently through much of the city itself along Baltimore Avenue.
Business US 63 was routed through Kirksville's downtown. It was decommissioned in 2001 and 2002 after plans for a bypass route around Kirksville were shelved. As a consequence, this sign assembly no longer shows Business Route 63.