Archaeology tells us that men first walked trails along the Eno long before recorded history. Indians of the Eno, Shakori, and Occoneechee tribes lived along the river when the first European explorers passed through. Some of the tribes merged in the late 17th century and established a village near present day Durham. Settlers moved in during the mid 1700's to set up farms and gristmills. More than 30 mills were located along the length of the Eno.
Efforts to establish Eno River State Park started in 1965, when the city of Durham proposed building a reservoir in the river valley. A group of concerned citizens led a campaign to save the Eno and formed the Association for the Preservation of the Eno River Valley. The association proposed a state park be established and, in May of 1972, the state of North Carolina approved the idea. The city of Durham withdrew its efforts to construct the reservoir and in 1975 the state, with help from the Eno River Association and the Nature Conservancy, opened the park with more than one thousand acres of land.