William Lewis III was born in Northern Ireland around 1730 and was about six years old when his father, William Lewis, Jr. moved the family to the Black River area in Southeastern North Carolina. He married in 1748 (wife's name unknown) and they had six sons: William, Thomas, Jacob, Benjamin, John, and Frederick.

William Lewis III was a farmer and produced turpentine and tar. He was also a surveyor and, with his brother Jacob, laid out a road from North Central New Hanover County to the Northwest Cape Fear River. He lived all his life in Northern New Hanover County (now Duplin County) and died there in 1800, almost 70 years old.