Waleska was incorporated in 1889, but the area was settled years earlier, primarily by the Reinhardt, Sharp, Rhyne and Heard families. A store, cotton gin and tobacco factory were in operation at the crossroads by 1856, and a post office was added to the store soon after. For many years the name of the post office was spelled "Walesca", but was changed to its current form to prevent confusion with another town.

The town was named after Warluskee, the daughter of an Indian Chief who lived in the area. When Warluskee was moved to the West along with her people, her friends, Mr. and Mrs. Lewis W. Reinhardt named their settlement in her honor.

Industry in Waleska in the past included gristmills, lumbering, tobacco, manufacturing and some mineral development. The lumber industry is still active in the area, as is agriculture.

The chief "industry" of the town, however, has always been Reinhardt College, and Waleska has come to be regarded, almost exclusively, as a college town.