The Kansas City Mule and St. Louis Mule were a pair of 283-mile (455 km) passenger trains operated by Amtrak running between St. Louis and Kansas City, Missouri as part of the Missouri Service train network. Also operating over this route was the Ann Rutledge, which originated in Chicago. In January 2009, Amtrak consolidated these trains under the name Missouri River Runner.

Amtrak introduced the two trains on October 26, 1980, in partnership with the state of Missouri, which provided a yearly subsidy of $484,000. The Mules supplemented the Ann Rutledge, which provided a daily round-trip between Kansas City and Chicago via St. Louis. Contemporary news accounts referred to the combined service as the "Missouri Mule", although Amtrak timetables used the individual names. Eastbound the train was known as the St. Louis Mule; westbound the Kansas City Mule.

The Mule's original schedule included intermediate stops at Kirkwood, Jefferson City, Sedalia and Warrensburg. Amtrak added Lee's Summit and Washington as flag stops in April 1981 on a one-year trial basis; Lee's Summit was retained in 1982 while Washington was dropped late 1981 in favor of Independence. Amtrak reinstated Washington on the October 29, 1995 timetable for another one-year trial period; this time Amtrak retained the stop. Hermann became a permanent stop on September 28, 1991. Trains had previously stopped only during Hermann's annual Maifest and Octoberfest.

Between April 29, 1984 and November 4, 1993 the Mules operated with the River Cities, a St. Louis section of the City of New Orleans. Additional cars were added between St. Louis and Carbondale, Illinois, which it connected with the New Orleans-bound train. A funding crisis caused Amtrak to discontinue the Mules between April 1 and July 1, 1995.

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