Middletown is a census-designated place (CDP) in Lake County, California, United States. Its population was 1,323 at the 2010 census, up from 1,020 at the 2000 census. Middletown was given its name because it is halfway between Lower Lake and Calistoga which is 17 miles (27 km) to the south. At one time, the community was known as Middle Station, and was a halfway point on the stagecoach route over Mt. St. Helena from Calistoga to Lower Lake. The first house was built at the site by J.H. Berry in 1870.

The town began in 1871. The Middleton post office opened in 1871 and changed its name to Middletown in 1875. Middletown enjoyed a robust quicksilver (mercury) mining industry through the end of the 19th century. By the early 1900s, cattle and sheep ranching were prominent, along with some limited pear and walnut production.

A resort economy sprung up around the various natural springs, and the area around Middletown attracted vacationers from the Bay Area through the 1950s. As travel costs decreased, tourism to the resorts diminished as patrons were able use air travel to vacation in more far flung places. Many of the resorts closed in the 1960s. In the 1970s and early 1980, exploitation of nearby geothermal energy resources brought an influx of workers into the local economy. Electrical power plants powered by "steam wells" were built in the mountains above Middletown. As housing prices in the Bay Area increased in the late 20th century, Middletown and nearby Hidden Valley Lake enjoyed a population boom as commuters moved to the Middletown area looking for affordable housing; keeping their jobs 50 to 100 miles away in Santa Rosa, Napa, and San Francisco. Middletown is currently populated primarily by commuters and retirees, enjoying a modest tourist trade based primarily on Harbin Hot Springs and the Twin Pine Casino located on the local Rancheria south of the town.