His education was in the local public schools.
After serving an apprenticeship of three years (1828 - 31) on the Cincinnati Gazette, Campbell took over the Hamilton Intelligencer, which heartily championed the cause of Henry Clay and the Whig party. While engaged with this weekly paper, he found time to study law and in 1835 was admitted to the bar. His practise and reputation as a lawyer grew rapidly.
In 1848 he was elected to Congress as a Whig, and for four consecutive sessions he was reelected. In 1858 he and C. L. Vallandigham fought for the support of the Miami Valley. Each claimed the victory, but the seat was awarded to Vallandigham by the House of Representatives. The high point of Campbell's career in Congress was his chairmanship of the Committee of Ways and Means in the Thirty-fourth Congress. In the great debates over slavery he displayed considerable force as a speaker, particularly in his opposition to the repeal of the Missouri Compromise. On the outbreak of the Civil War he served for a time as colonel of the 69th Regiment of Ohio volunteers, but ill health compelled him to leave the service. Although not in Congress, he opposed the Congressional program of reconstruction. He was a delegate at the Philadelphia Union convention and at the Soldiers Convention at Cleveland in 1866. President Johnson appointed him minister to Mexico at a time when Secretary of State Seward was trying to compel Napoleon III to recall his troops, by diplomatic rather than military pressure. The dogged resistance of the republicans of Mexico, led by Juarez, had won the admiration of the people of the United States. Although Campbell was appointed minister in May 1866, it was not until November that he departed on his mission to the Juarez government, located somewhere in northern Mexico. To make his mission more significant diplomatically, Gen. W. T. Sherman accompanied him. They found the coast towns still in the hands of Maximilian and failed to get in touch with Juarez. Campbell for the time being set up his "Legation" at New Orleans. Gideon Welles, secretary of the navy, wrote in his diary, "The Minister, with his thumb in his mouth, stood off, went up the coast, where Sherman left him. The whole business turns out a faux pas, a miserable, bungling piece of business". The refusal of Maximilian to leave Mexico following the withdrawal of the French forces had by this time become the chief difficulty in the Mexican situation. Seward repeatedly ordered Campbell to depart for his post of duty with the Juarez government, but Campbell, who found his duties irksome, pleaded ill health and private business as reasons for delaying. Seward practically forced his resignation, June 15, 1867. Campbell now found himself so thoroughly out of accord with the Republican party's program, both political and economic, that he withdrew his allegiance and in 1870 ran for Congress and was elected on the Democratic ticket. In 1872 he actively supported Greeley for the presidency. The document framed by that body did not meet with his approval and he aided the forces which accomplished its rejection. In his last years he frequently spoke and wrote in behalf of various movements for economic and political reform.
Over his political career he was elected as a Whig, Republican, Know Nothing, and Democrat.
He ran unsuccessfully as a Whig candidate for election in 1840, 1842, and 1844 to the 27th, 28th, and 29th Congresses. He was elected as a Whig in 1848 from Ohio's 2nd District to the 31st Congress and was re-elected in 1850. Following redistricting after the 1850 census, he found himself in Ohio's 3rd District but was successful in being again elected as a Whig in 1852. With the collapse of the Whigs, he ran as an Opposition Party candidate in 1854 and was elected to the 34th Congress. He became chairman of the powerful House Committee on Ways and Means.
He was a member of the United States House of Representatives from Ohio, member of the Ohio Senate, a member and vice-president of the third Ohio constitutional convention.
He was married to Jane H. Reily, daughter of John Reily.