In 1803, United States acquired from France the 828,000-square mile Louisiana Purchase, the former French lands west of the Mississippi River, for 2.83 cents per acre.

In the 1830s, the United States conducted Indian Removal of the Five Civilized Tribes from the Southeast region, to extinguish their land claims and allow European-American settlement in the area.

They were given lands in what was called Indian Territory west of the Mississippi River, mostly in present-day Oklahoma.

This part of Kansas was included at the time in the Cherokee Neutral Lands, and the county was named after this tribe.

Settlers began to move into the territory, with violence breaking out between supporters of slavery and those who wanted to abolish it.

For most of its history, Cherokee County had more of a Democratic lean in presidential elections than the rest of the state, particularly before 1968.

† means a community is designated a Census-Designated Place (CDP) by the United States Census Bureau.

The cities of Baxter Springs, Columbus, Galena, Scammon, and Weir are considered governmentally independent and are excluded from the census figures for the townships.