Caldwell was born on June 4, 1817, in Saint Clairsville, Ohio, the son of James Caldwell, a member of the House of Representatives from 1813 to 1817, and Anne Booker Caldwell. His uncle Alexander Caldwell, of Wheeling, served as a U.S. District Court judge from 1825 until 1839. Caldwell received an AB from Washington College (later Washington and Jefferson College) in Washington, Pennsylvania, in 1836 and a BL from Harvard University in 1838. He settled in Wheeling to practice law and on August 16, 1839, married Martha Baird. They had three sons, five daughters, and one other child who died in infancy. On August 16, 1860, approximately a year after his wife died, Caldwell married Alice Wheat, of Wheeling. They had two sons and three daughters. Caldwell’s namesake son by his first wife served as attorney general of West Virginia from 1885 to 1893.
Caldwell was elected mayor of Wheeling in January 1850, reelected in 1851, and won the office again in 1856 and 1857. In 1856 he defended the right of Virginia’s small Republican Party to meet in Wheeling and denounced the violence that resulted from the controversial assembly. Like many other public men from western Virginia, Caldwell, who had been a Whig, believed that eastern politicians slighted the interests of the western counties. His developing antislavery positions estranged him even more from the easterners. Caldwell moved from the Whig Party’s support for white workers and free labor into opposition to slavery and eventually into the Republican Party. In 1857 he was elected to a four-year term in the Senate of Virginia from the district composed of Brooke, Hancock, and Ohio counties. He was appointed to the Committee for Courts of Justice and the minor Committee to Examine the Clerk’s Office, and two years later he served on the same two committees as well as the important Committee on Finance and Claims. The unreservedly outspoken Caldwell endorsed and voted for bills to ameliorate the condition of slaves, circulated copies of Hinton R. Helper’s antislavery book, The Impending Crisis of the South: How to Meet It (1857), and denounced slavery and slaveholders. Richmond newspapers branded him a dangerous abolitionist, and slave owners threatened him with physical violence.
In 1860 Caldwell chaired the small Virginia delegation to the Republican National Convention in Chicago, where he supported Abraham Lincoln for president. Caldwell was attending his last session of the Senate of Virginia in Richmond when the secession convention began its deliberations in February 1861. That spring he joined western delegates in initiating the meetings that led to the creation of West Virginia. Caldwell did not participate in the formation of the new state, however, because on August 12, 1861, Lincoln appointed him U.S. consul in the kingdom of Hawaii. Caldwell was stationed at Honolulu from November 1, 1861, to January 7, 1867, when, at the insistence of the U.S. minister to Hawaii, the secretary of state suspended him for collusion in a scheme to enrich himself and his son-in-law by overcharging the government for services rendered. When he was suspended the consul’s accounts were also in arrears almost $4,000. Caldwell returned to Wheeling, where he died on May 3, 1868, and was buried in the local Mount Wood Cemetery.