Lewis Davis Campbell was born in Franklin, Ohio, the son of Samuel Campbell (1781-1846) and Mary Small (1786-after 1882). His education was in the local public schools. He was apprenticed to learn the art of printing from 1828 to 1831, and was afterward assistant editor of the Cincinnati Gazette. He published a Clay Whig newspaper in Hamilton, Ohio from 1831 to 1835 (Hamilton Intelligencer). During this time, he read the law and was admitted to the bar in 1835. He practiced law in Hamilton until 1850, after which time he engaged in agricultural pursuits.

Lewis Campbell married Jane Reily on January 5, 1836 in Butler County, Ohio.

He was a director and secretary of the Hamilton and Rossville Hydraulic Company, formed in 1841 for the purpose of building a canal through Hamilton to provide water power to local companies. He was an incorporator and president of the Cincinnati, Hamilton and Dayton Railroad Company which was constructed between 1846 and 1852.

He ran unsuccessfully as a Whig candidate for election in 1840, 1842, and 1844 to the Twenty-seventh, Twenty-eighth, and Twenty-ninth Congresses. He was elected as a Whig in 1848 from Ohio's Second Congressional District to the Thirty-first Congress and was relected in 1850. Following the redistricting after the 1850 census, he found himself in Ohio's Third Congressional 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 (Know-Nothing) candidate in 1854 and was elected to the Thirty-fourth Congress, in which he became chairman of the powerful Committee on Ways and Means. In the election of 1856, he claimed election and presented credentials as a Republican Member-elect and served from March 4, 1857, to May 25, 1858. However, his election was successfully contested by Clement L. Vallandigham who took his seat on May 26, 1857. Campbell ran against Vallandigham in the election of 1858, but Vallandigham was returned to office.

Lewis Campbell served in the Union Army as colonel of the Sixty-ninth Regiment, Ohio Volunteer Infantry, in 1861 and 1862, when he resigned on account of failing health.

President Andrew Johnson appointed Lewis D. Campbell as Envoy Extraordinary and Minister Plenipotentiary to Mexico on May 4, 1866. He was accompanied by General William Tecumseh Sherman. Campbell was instructed to tender to President Benito Juárez the moral support of the United States, and to offer the use of our military force to aid in the restoration of law. The occupying French forces of Maximillian had Juarez' government on the run, and Campbell failed to reach them. Campbell served until June 16, 1867, when he resigned and returned to resume his elective political career.

Campbell was elected to the Ohio Senate in 1869 and resigned in 1870 to take his seat in Congress, after being elected as a Democrat to the Forty-second Congress. He declined to run for reelection in 1872. He was a delegate to the third Ohio State constitutional convention in 1873, after which he resumed his agricultural pursuits.

His nephew, James E. Campbell later held the seat from the third district for one term (1885-7).

Lewis Davis Campbell died in Hamilton, Ohio, where he is interred in Greenwood Cemetery.