Born in Frederick County, Virginia, Campbell moved to eastern Tennessee and then to Kentucky with his parents. After studying medicine at Transylvania University, Campbell moved to Ohio in 1803, settling in Adams County a year later. He served in the Ohio House of Representatives from 1807 until 1809-12-12, when he resigned his position to be a U.S. Senator. An early anti-slavery campaigner, he had been unsuccessful in his candidacy for the U.S. Senate in 1808, but won a special election to the state's other seat a few months later and served from 1809–1813. He again served in the State House in 1819 and from 1832–1833, and in the Ohio State Senate from 1822-1824. He ran unsuccessfully for the governorship in 1826.