The town of White Sulphur Springs is named for its famous mineral springs, whose curative powers were first reported in 1778. According to one legend, in that year rheumatism sufferer Amanda Anderson was brought to the springs in a litter slung between two horses and left riding horseback after a few weeks' treatment. Her family had heard that Indians believed the strong-smelling water had healing properties. Many others came to the springs, first camping in tents then staying in rustic cabins. White Sulphur developed as one of the most fashionable of the southern spas in the antebellum period. Dr. John J. Moorman, who doctored the summer crowds from 1838 to 1883, wrote in his memoir of "the most highly medicated and efficient mineral water of its class in America, if not in the world." Modern chemical analysis shows the water to be rich in sulfate, calcium, bicarbonate and other minerals.

White Sulphur Springs was a Civil War battleground on August 26-27, 1863. Confederate forces under Col. George S. Patton, grandfather of the famous World War II general, forced Union troops under Gen. William W. Averell to withdraw.

White Sulphur Springs in Greenbrier County is the site of The Greenbrier resort. The community that developed around the hotel, known earlier as the "Old White," was incorporated as the town of White Sulphur Springs in 1909. Today, the town is located east of Lewisburg on Interstate 64 at an elevation of 1,980 feet. Both the town and resort were badly damaged during the deadly 2016 flood. In 2020, White Sulphur Springs had a population of 2,231, a 33.8 percent decline from its 1980 peak of 3,371.