William Houston, Sr., (d. c1795) was a Duplin County physician, apothecary, enslaver, and local political leader. In 1755, he joined other merchants, traders, and planters in petitioning the Board of Trade for relief on trade restrictions. Houston represented Duplin in the colonial Assembly from 1749 to 1762. Later during the American Revolution he was pro-independence and was the chairman of the Duplin County Court Martial Committee, which was responsible for finding and punishing the area's loyalists.