Born in Hillsborough, NC in 1770, Robert was the second son of the two sons of James and Elizabeth (nee unknown) Guthrie, Sr. His parents and his sister Ann Guthrie and elder brother James removed to the American colonies from Ireland between 1765-1770 arriving in Baltimore, MD. By 1770 the family was located on their farmland just outside Hillsborough, Orange County, NC where Robert was born. He grew up with his brother James and his 6 sisters Ann, Mary, Margaret, Martha, Jean and Elizabeth. In January of 1791, Robert married Mary Smith, the daughter of Andrew and Elizabeth (Kerr) Smith, Sr. Mary was the sister of Jane Smith who married Robert's brother James the following month. Both brothers and their wives moved to Tennessee and located in Sumner County between 1791-1800.

In 1819, Robert was ordained as a Presbyterian Minister of the Gospel. He and his wife Mary raised their children in Sumner County, TN. In 1831, after two of their sons had moved to MO, the parents followed, reamining there for the rest of their lives. Sons James, Eli and Allen also became ministers. They had eleven known children:

1. Annie Guthrie, born 1791, probably in Hillsborough, Orange County, NC; married William Burney in Sumner County, TN in 1812; died before. December 1869

2. James Smith Guthrie, born 1795 in TN; married Electa Austell about 1830 in Elyton, AL; died in TX in 1853

3. Andrew Harvey Guthrie, born in Sumner County, TN 27 August, 1797; first married Margaret Stewart Kirkpatrick 6 April 1820; married second Jane Stewart Kirkpatrick 7 March 1836; died 09 October, 1864 in Perry County, TN

4. Robert Wesley Guthrie, born in Sumner County, TN 02 April, 1799; married Nancy Foster 07 October, 1819 in Sumner County, TN; died 07 August, 1872

5. Eli Guthrie, born in Sumner County, TN in 1801; married Eliza Caldwell in Sumner County 23 February, 1830; died 17 December, 1837 in Dewitt, Carroll County, MO

6. Betsy Guthrie, born in Sumner County, TN in 1803; married George Wills in Sumner County on 09 April, 1823; died in 1836 in Chariton County, MO

7. Sarah Guthrie, born in Sumner County, TN in 1805; first married Thomas Culbertson on 22 December, 1825; married second Abram Cash on 30 June, 1844 in Chariton County, MO; died after 1844 in MO

8. Mary Harriett Guthrie, born in Sumner County, TN in 1809; married first Matthew T. Wills in Sumner County, TN on 10 September, 1825; married second Frank Moss in MO between 1825-1844; married third Abram Cash in MO after 1844

9. Jane Guthrie, born in Sumner County, TN in 1811; married James Capper in Sumner in 1832; died in MO before 1869

10. Allen Washington Guthrie, born in Sumner County, TN on 26 November, 1813; married first Elizabeth Ann Young in Callaway County, MO on 06 September, 1838; married second Margaret A. Smith in Buchanan County, MO on 17 April 1856; died 13 April, 1891 in Macon County, MO

11. Nancy Kerr Guthrie, born in April of 1816 in Sumner County, TN married Daniel Culbertson in 1833 in Chariton County, MO; died in 1882 in Chariton County, MO