The land was ceded after prolonged negotiations with the Chickasaw Indians in which the United States was represented by Andrew Jackson and Isaac Shelby, while the Chickasaws were represented by their chiefs, head men, and warriors including: Levi Colbert, his brother George Colbert, Chinubby, and Tishomingo.

[2][3] Although claimed as part of Kentucky at its statehood in 1792, the land did not come under definitive U.S. control until 1818, when General Andrew Jackson and ex-Kentucky governor Isaac Shelby, representing the United States federal government, purchased it from the Chickasaw Indians through several treaties, including the Treaty of Tuscaloosa.

Due to changing demographics, most counties in the Purchase in the early 21st century have populations that are overwhelmingly white.

[citation needed] During the Civil War, the Purchase was the area of strongest support for the Confederate cause within Kentucky.

[5] In 1907, Fulton County judge Herbert Carr declared in a speech that the Mayfield Convention adopted a resolution for secession, and a historical marker in front of the courthouse also proclaims this as fact.

Historian Berry Craig states that the convention believed the whole of Kentucky would eventually secede and make unnecessary a separate resolution for the Purchase to break away.

Together with the portion of the Tennessee River north of Kentucky Dam, it forms the eastern border of the Purchase.