Mayesville grew up around a railroad depot built in 1853 by the Wilmington and Manchester Railroad on land owned by Matthew Peterson Mayes, known as "Squire," a Virginian born in 1794 who settled in the Sumter District after marrying Martha Bradley, later married Henrietta Shaw, built a home near the site of the future town, invested in its growth, and encouraged its prosperity. During the Civil War, Union troops moving through Sumter District toward Bentonville, NC, found rail cars in Mayesville and destroyed them along with the depot, rails, and a bridge. The town recovered from the ravages of war and by the turn of the 20th century had become a prosperous agricultural center in this part of Sumter County, with a hotel, two banks, furniture and hardware stores, a post office, five physicians, an undertaker, several churches, and new schools. Mayesville's prosperity began to unravel when the highway to Sumter was paved in 1922, and this, combined with the Great Depression, slowly eroded the town's commercial center, though today it is experiencing a revival.