Wayne County received its name in honor of the Revolutionary hero, General Anthony Wayne, as did its county seat, Waynesboro. It was created by act of the General Assembly of Mississippi territory, December 21, 1809, and embraced the western, or Mississippi portion, of the old county of Washington, established in 1800 by proclamation of Governor Sargent and perpetuated in the present county of that name in Alabama.

The act of 1809 which created Wayne County recites that Washington shall be divided as follows:
“beginning on the line of demarcation, where the trading road leading from the Choctaw nation to Mobile crosses the same, thence along said trading road to the present Choctaw boundary line, thence along said boundary line to Pearl River, thence down the same to the line of demarcation, and with the same to the place of beginning, all to be called the county of Wayne”