The region was created in late 2021 when the Lewis and Clark Trail Heritage Foundation reorganized its structure into regions. The Southern Prairie Region covers six states: Missouri, Kansas, Texas, Oklahoma, Arkansas, and southwestern Illinois.
At the time of restructuring, some smaller chapters decided to dissolve while other chapters remained in existence within their region and sometimes hold events primarily for members in their chapter areas.
The new Southern Prairie Region includes two already existing chapters: the Greater St. Louis Chapter and the Missouri-Kansas Riverbend Chapter in northwest Missouri and eastern Kansas.