Between the years of 1763 and 1783 the area which is now Barbour County was part of the colony of British West Florida.

[3] After 1783 the region fell under the jurisdiction of the newly created United States of America.

The Muscogee Creek Confederacy was removed to territory west of the Mississippi River.

The fertile land was developed by southern migrants as large cotton plantations dependent on slave labor.

Due to the number of slaves, the population was soon majority black, a proportion that continued for decades.

In the 21st century, the population has a slight white majority, but blacks make up more than 46% of the residents, which results in highly competitive politics.

The county seat was moved in 1834, after an eleven-member committee selected Clayton because of its central geographic location.

By the 1870s, the city of Eufaula had surpassed Clayton in size, sparking debate about whether the county seat should be moved to the county's commercial center or remain at its geographic center.

As of the 2020 United States census, there were 25,223 people, 9,345 households, and 6,187 families residing in the county.

26.50% of all households were made up of individuals, and 12.10% had someone living alone who was 65 years of age or older.

Wallace Community College operates a campus located in Eufaula.

Marking changes in 20th-century politics, Chauncey Sparks, the Wallaces, and Jere Beasley were not from the planter elite.