Isaac Harmon Farmhouse is a historic farmhouse located near Millsboro, Sussex County, Delaware. It was built about 1845, and is a two-story, four-bay, single pile, wood frame dwelling clad in clapboard. It has a gable roof pierced by interior end brick chimneys. It was one of the first properties in the Indian River community to be owned by a family of the Nanticoke Indian Association. Isaac Harmon was one of the leaders in the Nanticoke Indian Association separatist movement of the 1880s, which grew out of the mixed-race community of Delaware Moors.
It was added to the National Register of Historic Places in 1979.