Born in the Kingdom of Ireland, Smith was in his late twenties when he arrived in South Carolina in the months immediately following the end of the Revolutionary War.
He took the oath of allegiance to the Government of the United States on July 31, 1784, and began to participate in his adopted country's political activities, serving as a member of South Carolina House of Representatives from 1789 to 1799 and in the South Carolina Senate in 1800.
During this time in his life, Smith lived at the Capers-Motte House in Charleston, South Carolina.
O'Brien Smith was in his mid-fifties when he died in South Carolina, nearly three decades after arriving in the United States.
He was interred in the burial ground of the colonial Chapel of Ease of St. Bartholomew's Parish, Colleton County, near Jacksonboro.