Born in Ireland about 1765, James was the eldest son of James and Elizabeth (nee unknown) Guthrie, Sr. With his parents and (probably) his sister Ann Guthrie, James removed to the American colonies between 1765-1770 arriving in Baltimore, MD. By 1770 the family was located on their farmland just outside Hillsborough, Orange County, NC where James grew up with his brother Robert and 6 sisters Ann, Mary, Margaret, Martha, Jean and Elizabeth.

In 1791, James married Jane Smith, the daughter of Andrew and Elizabeth (Kerr) Smith, Sr. Jane was the sister of Mary Smith who had married James' brother Robert earlier in the year. Both brothers and their wives moved to Tennessee and located in Sumner County between 1791-1800. They had eleven known children:

1. James Guthrie, III, born 1791-1793 in NC or TN; died 5 December 1814 (War of 1812)

2. David Guthrie, born 1791-1793 in NC or TN; probably died in TN before 1820

3. Sally Guthrie, born 1791-1803 probably in TN; married David Carr/Kerr in Sumner County in 1819; died after 1870 in Maury County, TN

4. Robert Guthrie, born 17 March 1793 in "NW Sumner County, TN"; married Acenith Motheral in Wilson County in 1820; died in Sumner County 29 May, 1853

5. Elizabeth Guthrie, born 22 March, 1799 in Sumner County, TN; married James Martin in Sumner County in 1818; died after 1873 probably in Sumner County

6. Joseph Guthrie, born 23 September, 1802 in Sumner County, TN; married Mary McNeely in Sumner County in 1826; died before 1873

7. William H. Guthrie, born 1803 in Sumner County, TN; died December 1872 in Clarkton, MO

8. Andrew H. Guthrie, born 1807 in Sumner County, TN; married Emily Wright in Sumner County in 1839 (his 2nd marriage); died after 1880

9. Eunice Jane Guthrie, born 08 October, 1809 in Sumner County, TN, married Alexander Latimer in Sumner County in 1829; died in Abingdon, IL 15 September, 1840

10. Lorena K. Guthrie, born between 1811-1815 in Sumner County, TN, married 18 January, 1837 Elvis Harder/Harden in Sumner County; died before 1873

11. Annie Guthrie, born 1812 in Sumner County, TN; married Richard Pond in Sumner County 13 August, 1832; died 12 December, 1862 in Sumner County, TN