After obtaining a public school education, he studied law, was admitted to the bar at Covington, Ky., in 1858, and at age 24 was elected to the Kentucky legislature, where he served in the lower house, 1859-1861, and in the upper house, 1866-1869.
He was instrumental in keeping Kentucky from seceding during the Civil War. He was elected lieutenant-governor of Kentucky by the Democrats for the term 1871-1875, and to the United States House of Representatives in 1876; and in 1890, after serving six terms in the House, during which he was speaker for six years (1883-1889), he was elected to the Senate. In 1893 President Grover Cleveland appointed him secretary of the treasury. Carlisle supported a low tariff, was an unswerving supporter of the gold standard, and, during the 1896 presidential campaign, advocated "sound money" in opposition to the free-silver program of the Democratic nominee, William Jennings Bryan. In 1897, after the defeat of the Democrats, Carlisle went to New York City, where he practiced law.