Millions of years ago, a shallow sea covered Ohio, depositing fossil-rich limestone and dolomite bedrock.  Fertile soils, left behind by glaciers thousands of years ago, created a productive land that attracted early Native Americans, including the Miami people, and settlers.

In 1797, Matthew Hueston, after serving with General "Mad" Anthony Wayne in the Indian wars, bought land for a farm in Butler and Preble counties. He left a remnant of the woods standing for his descendants.

When the last of the Huestons died in the 1930s, Morris Taylor, a conservationist, purchased the woods and held it in trust, while Cloyd Acton, a Preble County legislator, influenced the state legislature to buy the land in 1941. Hueston Woods was designated a state forest, and in 1945, money was appropriated to buy additional land.

In 1952, the Oxford Honor Camp was located here, housing honor-status inmates for 12 years. In the summer of 1956, an earthen dam was completed across Four Mile Creek, creating Acton Lake. Hueston Woods became a state park in 1957. The old-growth forest was added to the National Registry of National Landmarks in 1967, and became a state nature preserve in 1973.