Admitted to the Kentucky
bar in 1817, Guthrie began his private legal practice in Bardstown. In 1820,
Governor John Adair appointed Guthrie as
Commonwealth's Attorney for
Jefferson County, Kentucky, whereupon Guthrie relocated to what was then the town of
Louisville. The effort failed, but Guthrie was elected to the town's board of trustees, and later became its chair.
Kentucky politician Jefferson County voters elected Guthrie, who ran as a
Democrat, to the
Kentucky House of Representatives in 1827. In his first year, he chaired the
Internal Improvements Committee. In this capacity, he promoted construction of a number of roads and canals, as well as a
railroad connecting Louisville to
Frankfort. He served on the Finance and Education Committees. In 1836, a dispute arose among the medical faculty at
Transylvania University. Guthrie encouraged some of the disgruntled faculty members to relocate to Louisville and start the
Louisville Medical Institute, a precursor to the
University of Louisville. In 1843, Guthrie became the third president of Louisville Medical Institute. In 1846, the Kentucky General Assembly chartered the
University of Louisville, which subsumed the Louisville Medical Institute. Guthrie became president of the university on December 7, 1847, and served until his death. In 1845, he was a delegate to a convention on
internal improvements held in
Memphis, Tennessee, and chaired by
John C. Calhoun. Guthrie represented Louisville at the Kentucky Constitutional Convention of 1849. The major question the convention addressed was slavery. Guthrie owned enslaved persons, and believed that, if freed, the slaves would become vicious and ungovernable. Instead, Guthrie advocated adoption of a universal currency that would be convertible to
gold on demand. He encouraged more efficient processes in the Treasury Department as a whole, and required monthly, rather than quarterly, reports from
customs agents. He continued as the railroad's president through the Civil War, and after he became incapacitated in 1868 advocated the board's electing former Union General
William Tecumseh Sherman as his successor, although the board selected
Russell Houston in 1869. Meanwhile, Kentucky, delegates to the
1860 Democratic National Convention in
Charleston, South Carolina, favored Guthrie for the office of President. On the first of many ballots, Guthrie received 35.5 votes; by the thirty-ninth, he was up to 66.5, but still trailed the leading vote-getter
Stephen Douglas, by 85 votes. He received 5.5 on the second ballot, which finally saw Douglas attain the necessary majority. On this topic, he stated "I hate that word secession, because it is a cheat! Call things by their right names! The Southern States have... originated a revolution." At age 70, Guthrie was elected as one of Kentucky's six delegates to the
Peace Conference of 1861 in Washington, D.C., to devise means to prevent the impending
Civil War. Guthrie supported President
Andrew Johnson, opposed the
Freedmen's Bureau and the passage of the
Fourteenth Amendment. ==Death and legacy==