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 an Indian family. Isaac Harmon was one of the leaders in the Nanticoke separatist movement of the 1880s.