James Guthrie was born in 1792 in Bardstown, Kentucky. After studying the law and being admitted to the bar in 1817, he opened a private law practice and pursued a career in politics as a Democrat. After two failed attempts at serving in the state legislature, Guthrie became commonwealth attorney for Kentucky in 1820.

In 1827, Guthrie succeeded in becoming a state legislator, serving in Kentucky’s lower house until 1831, when he was elected to the state senate. During the nine years he was in that body, Guthrie served twice as Speaker pro tempore and made an unsuccessful bid for the United States Senate in 1835.

Guthrie later became president of the Louisville Medical Institute (1843-1846), and when it merged into the University of Louisville, he served as president of that institution (1846-1847). He then sat, in 1849, as a member of the Kentucky Constitutional Convention. Four years later, Guthrie was serving President Franklin Pierce as secretary of the treasury, a post he held until the end of the Pierce presidency in 1857.

Following his time in the cabinet, Guthrie turned his attention to railroads, an interest he had explored in the 1840s. He refused an offer from President James Buchanan to serve as secretary of the treasury, but he did attend the “Peace Convention” in 1861 in an attempt to ward off civil war. When hostilities erupted, Guthrie threw his support and the use of his railroads to the Union.

Following the war, Guthrie was elected to the United States Senate, resigning in 1868 due to ill health. He died in 1869.