The home's significance is not only its age and somewhat eclectic architectural style. Over its long history, the Parson Thorne Mansion has been home to several of the area's most influential citizens, including businessmen, religious leaders, and a city founder.
The home sits on a 1,750 Duke of York land patent known as Saw Mill Ridge which was granted to Henry Bowman in 1680. The earliest known resident on the land was Joseph Booth, who purchased 580 acres from the Bowmans in 1730. In the 1780s, Reverend Syndenham Thorne, from whom the home takes its name, purchased the property. An Episcopal priest, Thorne was one of the city's founders and is buried on the grounds.
In subsequent years, the mansion was home to a number of other prominent figures. John M. Clayton, who served as both a US Senator and Secretary of State, lived in the home for a time during his childhood. Dr. William Burton, a governor of Delaware, lived in the home for part of his term. Henry Fiddeman, a founder of the First National Bank of Millford, purchased the home in 1858.The home eventually became the property of the Millford Historical Society and was added to the National Register of Historic Places in 1971.