The Meeteetse area is rich in history with the expansive Pitchfork Ranch, famous as one the west's true cattle empires. It was the first cattle ranching operation of the Big Horn Basin, established in 1879 by Otto Franc. By 1900, thousands of cattle grazed along the Greybull River and Wood River Valleys. Pitchfork is also well-known for the fact the last known colony of an endangered species, the black-footed ferret, was found on its grasslands.

Noted outlaw Butch Cassidy lived in Meeteetse. In 1886, he signed a petition for the new bridge, and in 1894, he was arrested in front of the Cowboy Bar.