The area of Pottawatomie County was crossed by several trails in the early days, including the Oregon Trail laid out in 1842, Military Road in 1852, and Pike’s Peak Trail at the northern edge of the county.
The Indian mission at St. Marys, founded in 1848 by the Jesuits, is one of the earliest indications of white men settling in Pottawatomie County. The Kansas-Nebraska Act signed in 1854 made settlement legal.
In 1856 the legislature was petitioned to create Pottawatomie County, named for the Pottawatomie tribe of Indians. In February of 1857, Governor Geary appointed the 1st county officials.
The 1st city platted in the county was St. George in 1857. The first road laid out by the county was from the Rock Creek crossing south of Westmoreland to St. George in 1858.
The county seat originally was located at St. George before being moved to Louisville in the election of 1861. The county seat was moved again, by election in 1882, to Westmoreland.