The house was built by David Bradford, a successful lawyer and deputy attorney-general for Washington County, Pennsylvania who would later become a leader in the Whiskey Rebellion. It was the first stone house on South Main Street in Washington, Pennsylvania in 1788, which, by frontier standards, ranked as a mansion. The two-story building was built in the Georgian style, with dressed stone four-bay windows. The house has side hall entry with with a fanlight transom. The stairway was solid mahogany; the mantel-pieces and other interior furnishings, imported from Philadelphia, were transported across the Alleghenies at considerable expense. While restoring the house a secret underground passage was discovered leading to a nearby ravine. This tunnel was presumably used as an escape route in the event of an attack on the house.
Bradford and his family occupied the house only for 6 years, until 1794, when he fled following the Whiskey Rebellion.
By the 1930s, the building was in such disrepair that Charles Morse Stotz did not include the building in his The Early Architecture of Western Pennsylvania. However, by the book's 2nd printing in 1966, Stotz himself has led the rehabilitation. Among other extensive modifications, a storefront had added to the house.
In 1953, the Pennsylvania Historical and Museum Commission installed a historical marker noting the historic importance of the building. In 1959, the Pennsylvania Historical and Museum Commission assumed control of the house and supervised restoration of its eighteenth-century design. They installed furnishings of that that time in Pennsylvania that they felt reflected Bradford's place in society. A management agreement was signed in 1982, turning the management of the Bradford House over to the Bradford House Historical Association. The museum is open from early May through mid December, giving group tours and hosting other special events.