Wilson was born Jeremiah Jones Colbath in Farmington, New Hampshire. In 1833 he had his name legally changed by the legislature to Henry Wilson. It is unknown why he changed his name. He moved to Natick, Massachusetts in 1833 and became a shoemaker. He attended several local academies, and also taught school in Natick, where he later engaged in the manufacture of shoes. He was a member of the state legislature between 1841 and 1852, and was owner and editor of the Boston Republican from 1848 to 1851.

Wilson was an unsuccessful candidate for election in 1852 to Congress. He was a delegate to the state constitutional convention in 1853 and was an unsuccessful candidate for Governor of Massachusetts in 1853. In 1855 he was elected to the United States Senate by a coalition of Free-Soilers, Americans, and Democrats to fill the vacancy caused by the resignation of Edward Everett. He was reelected as a Republican in 1859, 1865 and 1871, and served from January 31, 1855, to March 3, 1873, when he resigned to become Vice President. He was Chairman of the Committee on Military Affairs and the Militia and the Committee on Military Affairs. In 1861 he raised and commanded the Twenty-second Regiment, Massachusetts Volunteer Infantry.

Wilson was elected Vice President of the United States on the Republican ticket with President Ulysses S. Grant and served from March 4, 1873, until his death in the United States Capitol Building at Washington, DC. He had suffered from paralysis from 1873-75. Among his works are: History of the Anti-Slavery Measures of the Thirty-seventh and Thirty-eighth Congresses, 1861-64 (1864); History of the Reconstruction Measures of the Thirty-ninth and Fortieth Congresses, 1865-68 (1868); and an exceedingly valuable publication, History of the Rise and Fall of the Slave Power in America, (three volumes, 1872-77). He was interred in Old Dell Park Cemetery, Natick.