Appleton (Samuel) is born in New Ipswich, New Hampshire.

The son of Isaac and Mary (Adams) Appleton, Nathan Appleton comes to Boston in 1794 and soon opens a shop with his younger brother, Nathan. Their company, S & N Appleton subsequently becomes a successful seller of imported and domestic goods. Samuel marries Mary Lekain Gore in 1819 and the couple build a home at 40 Beacon Street. He subsequently invests successfully in the textile industry and railroads. After retiring from business , Appleton becomes involved in philanthropy and historic preservation. He dies in Boston in 1853.