The Mobile and Ohio Railroad was a railroad in the Southern U.S. The M&O was chartered in January and February 1848 by the states of Alabama, Kentucky, Mississippi, and Tennessee. It was planned to span the distance between the seaport of Mobile, Alabama and the Ohio River near Cairo, Illinois. On September 13, 1940, it was merged with the Gulf, Mobile and Northern Railroad to form the Gulf, Mobile and Ohio Railroad.

The Gulf, Mobile and Ohio was a Class I railroad in the central United States whose primary routes extended from Mobile, Alabama, and New Orleans, Louisiana, to St. Louis and Kansas City, Missouri, as well as Chicago, Illinois.