John Carlyle came to Virginia in 1741 as the representative of the English merchant William Hicks and built a business of his own. His commercial activities included trade with Britain and the West Indies, retailing in Alexandria, iron production, and blacksmithing. Marriage to Sarah Fairfax in 1747 strengthened his ties to a powerful Virginia family. He acquired extensive landholdings and became one of Alexandria's original trustees when the town was established in 1749.

Carlyle purchased lots near the river and market and built his stone house between 1751 and 1753. Its construction and the operation of his businesses depended on enslaved workers, including skilled artisans and agricultural laborers. His plantations and commercial enterprises made him a substantial slaveholder as well as a wealthy merchant. He also served as a Fairfax County justice and maintained connections with George Washington and other local leaders.

During the French and Indian War, Carlyle supplied Virginia's forces as commissary of stores. In 1755 General Edward Braddock used his house as headquarters and gathered colonial governors there to discuss the campaign against the French. Carlyle's correspondence records both the prominence this brought him and his dissatisfaction with the general's conduct as a guest. He continued in business and public affairs through the Revolutionary period and died in 1780. His letters and estate records document his commerce, civic service, family, and slavery.