The division was prompted by a substantial increase in the number of admiralty cases arising from traffic on the Mississippi River, which had followed an act of Congress passed in 1845 and upheld by the United States Supreme Court in 1851, extending federal admiralty jurisdiction to inland waterways.

[7] These disputes involved "contracts of affreightment, collisions, mariners' wages, and other causes of admiralty jurisdiction", and litigants of matters arising in St. Louis found it inconvenient to travel to Jefferson City for their cases to be tried.

The Central Division covers Benton, Boone, Callaway, Camden, Cole, Cooper, Hickory, Howard, Miller, Moniteau, Morgan, Osage, and Pettis counties.

The Southern Division covers Cedar, Christian, Dade, Dallas, Douglas, Greene, Howell, Laclede, Oregon, Ozark, Polk, Pulaski, Taney, Texas, Webster, and Wright counties.

The St. Joseph Division covers Andrew, Atchison, Buchanan, Caldwell, Clinton, Daviess, DeKalb, Gentry, Grundy, Harrison, Holt, Livingston, Mercer, Nodaway, Platte, Putnam, Sullivan, and Worth counties.

The Southwestern Division covers Barry, Barton, Jasper, Lawrence, McDonald, Newton, Stone, and Vernon counties.