Macon sits at the crossroads of two of Missouri's four-lane highways: Highway 63 and Highway 36 (the Chicago/Kansas City Expressway). Highway 63 is an important north-south artery linking southeast and northeast Missouri. Highway 36 is an east-west connection from Chicago to Kansas City. Macon is an hour's drive from Interstate 70 and is easily accessible to most major markets throughout the United States. To illustrate the accessibility Macon offers to northern Missouri, many government agencies, both state and federal, have regional offices here. Additionally, Gully Trucking serves the Midwest from its terminal in Macon.

Macon's airport is functional and efficient with a 4,150 foot, lighted runway, a full service fuel stop, airplane hangars and courtesy transportation. In addition, St. Louis Lambert Field and Kansas City International are both international airports within driving distance of 2.5 hours. To transport heavy goods, the Burlington-Northern and Santa Fe Railroads maintain service to Macon. Macon is within 60 miles of a duty-free terminal at the Missouri River for transporting by barge.

Macon was the first city in the State of Missouri to have total fiber optics to every home and business, provided by Chariton Valley Telecom. In addition, Chariton Valley Television hosts CVTV, a channel that  provides local information, coverage and special features to cable customers.

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