Set in the rural town of Hooterville, the show followed the goings-on at the Shady Rest Hotel, of which Kate Bradley was the proprietor. Her lazy Uncle Joe helped her in the day-to-day running of the business, while she served as a mediator in the various minor crises that befell her three daughters: Betty Jo, Bobbie Jo, and Billie Jo.
Other memorable characters included Charley Pratt and Floyd Smoot, the engineer and conductor of the Hooterville Cannonball, a steam-driven train run more like a taxi service. Sam Drucker ran "Drucker's Store, a favorite of Hooterville farmers because he would give credit, while the Pixley stores wanted cash. Another character was the unnamed canine companion of the sisters, referred to simply as "dog".