The George Mosse Stoney House traces its history back to the 1700s, as evidenced by a John Campbell painting finished in 1798, showing a different house on the lot. When it was acquired by Dr. George Mosse Stoney sometime around the early 1800s, the original house was replaced, according to the desires of his wife, Sarah Barnwell.

It is believed that the George Mosse Stoney House was built around 1823, as proven by some previous accounts. However, thorough examination of the house shows elements like hand forged nails and wooden pegs in sills that can be date back from the 1840s. It is also speculated that the structure was rebuilt or renovated around the time, and it could still have been originally constructed in the 1820s.