Yalobusha is a native American word meaning "tadpole place," and before the county which bears that name was formed, it was the home of both Choctaw and Chickasaw Indian tribes.
In 1816, General Andrew Jackson ordered the surveying of the Choctaw-Chickasaw Line. The line as surveyed then cut almost a perfect diagonal across the area making up the present day Yalobusha County. The Choctaws ceded their Mississippi lands to the United States in 1830 through the Treaty of Dancing Rabbit Creek. Two years later, the Chickasaw signed the Treaty of Pontotoc, ceding their lands to the United States.
In 1833, the Mississippi Legislature authorized the formation of 17 counties, including Yalobusha, on what had been Indian land.