John Lowry moved his family from Virginia and purchased land on Meridianville Pike in 1809. He was the contractor for Madison County's first courthouse in 1811. His grandson, John Tate Lowry, a leading merchant with Lowry, Hamilton and Company, constructed the house around 1859 utilizing wood from the original cabin. John Tate's son, Samuel, received his degree from Bellevue Medical College, New York, in 1873. Dr. Samuel Lowry, who returned to Huntsville and set up practice with Dr. Hawkins Westmoreland, was the fourth generation and last member of the family to occupy the house. In 1998, Harvie P. Jones, FAIA, prominent preservation architect, assisted the owners in the property's restoration.
The house, important for its nineteenth century blend of architectural styles, was added to the National Register of Historic Places on October 29, 2001.