Located at the center of Nemacolin, it was the hunting lodge of Pittsburgh businessman Willard F. Rockwell, who had it built in 1968.

The resort is named after Chief Nemacolin, a native Delaware Indian who in 1740 trailblazed a route through the Laurel Highlands mountains between what is now Cumberland, Maryland and Brownsville, Pennsylvania.

Joseph A. Hardy III, founder of the 84 Lumber Company, bought Nemacolin at an auction that year and reopened the complex as an upscale hotel and resort.

In 2009 Nemacolin's fine dining restaurant, Lautrec, received a Five Star rating from the Forbes Mobile Travel Guide and held that distinction until 2015.

In 2019, Churchill Downs Inc. bought the casino operating business for $100,000 from Eldorado Resorts (which had previously acquired Isle of Capri).