The New World land which became Houston County, Georgia, was first described in journals of the Hernando De Soto expedition, 1540. The Spanish explorers traveled along the Ocmulgee River and camped at Westlake, near present day Bonaire. These lands were then occupied by aboriginal people, probably ancestors of the Creeks. Natives in these agrarian communities cultivated corn and other crops, and hunted to provide their sustenance Through the controversial Indian Springs Treaty of 1821, the Creek Indian Nation ceded lands from which Houston County was formed. Originally county boundaries extended east to west from the Ocmulgee's western shore to the eastern shore of the Flint River; its northern boundary extended due west from a site on the Ocmulgee opposite Fort Hawkins to the Flint River and its southern boundary extended from the Ocmulgee opposite the town of Hartford due west to the Flint. At the time, Houston County was one of the largest counties in Georgia; however, shortly after its formation, in 1822, the size was reduced when the counties of Upson, Crawford and Bibb were carved from it. Additional land losses occurred with the formations of Pulaski County in 1828, Macon County in 1837 and finally Peach County in 1924.

At its formation in 1821, the county was named Houstoun in honor of Governor John Houstoun by act of the General Assembly (it is not known when or why the second letter "u" was dropped from the spelling). Residents are quick to correct its pronunciation by the unknowing, from the familiar "hugh-ston" of Texas fame to that as it should be, "house - ton".

Early settlers were eager to occupy the lands of the newly created county with its rich soil, abundant water, moderate temperatures and native forest. The land was surveyed and then dispersed by a land lottery in 1821. Records of those lucky individuals drawing lots are found in the Official Registry of the Land Lottery of 1821, readily available to researchers.

Some early Houston County settlements were Wilna, Hayneville and Henderson. The latter two are still on present-day maps, but time has passed by Wilna, which was located near Houston Lake. The small community of Wattsville is now known as Perry, the seat of county government since the county's formation. Perry is conveniently located on I-75 about a two-hour drive south from Atlanta.