Named in memory of U.S. Naval Captain James Lawrence, who is best known for his dying words “Don’t Give Up the Ship,” Lawrence County was established on December 22, 1814 and was one of the fourteen territorial colonies prior to the founding of the State and was the twelfth county. During Lawrence County’s long, roller-coaster like history, there have been three (3) Mississippi Governors with strong Lawrence County ties. They were Charles Lynch, Hiram Runnels, and Andrew Longino. Other notable natives include Rod Paige, former Secretary of Education under President George W. Bush, the late blues man J.B. Lenoir, as well as blues man Byther Smith who continues to play.

The treaty of Mount Dexter in 1805 between the United States and the Choctaw Indians opened the floodgates for settlers in the Pearl River area—only the Gulf Coast and Natchez areas were settled prior to the Pearl River area. This new land offered fertile, river bottom land which was quickly bought by the more affluent in the region and served to draw settlers from all over the country. The Pearl River provided a quick and direct route to the New Orleans markets for cotton and other goods, while simultaneously providing a return corridor for much need supplies. Along with St. Stephens Road being built through Monticello, which was the main east-west corridor between Natchez and Fort St. Stephens (north of Mobile, AL), Lawrence County, for a time, was as prosperous as any other area in Mississippi.