Wilson moved to Natick, Massachusetts, where he apprenticed as a shoemaker before working at the trade for himself. He continued reading widely and became a member of the local debating society. On a trip to Virginia for his health, he saw slaves being traded in Washington, D. C., and resolved to lend his efforts to abolish slavery. Back in Natick, he resumed his shoe trade and by 1839 had saved enough money to buy a shoe factory. In 1840 he married Harriet Malvina Howe and they had one son, who would later serve in the Civil War as the lieutenant-colonel of a black regiment.

In 1840, Wilson entered politics, supporting the Whig presidential candidate, William Henry Harrison, and was himself elected to the Massachusetts state House of Representatives as a Whig. Wilson served in either the state House or Senate during 1841-1847 and 1851-1853. In 1845 he participated in a convention protesting the expansion of slavery via the annexation of Texas, and was chosen, along with John Greenleaf Whittier, to present the convention's petition to Congress.

When the 1848 Whig National Convention nominated a slaveowner, General Zachary Taylor, for president and refused to take an anti-slavery stance in their platform, Wilson helped lead a minority faction in establishing the Free Soil party. From 1848 to 1851 he edited a key organ of the new party, the Boston Republican, which was instrumental in electing anti-slavery advocate Charles Sumner to the U. S. Senate. Wilson himself served as state senate president in 1851 and 1852, and was an unsuccessful Free Soil candidate for governor in 1853.

In 1854 Wilson joined other anti-slavery proponents in the American (Know Nothing) party, which they hoped to liberalize away from its nativist views. He was, however, roundly criticized for that decision. The next year, when the American National Council evaded the slavery issue, Wilson led a revolt that brought about the rapid decline of the party. In January 1855 the Massachusetts state legislature, dominated by American party members, had elected Wilson to fill the U. S. Senate seat opened by Edward Everett's resignation. In his inaugural speech on the Senate floor, Wilson endorsed the abolition of slavery in areas under federal jurisdiction-the District of Columbia and the western territories-and the repeal of the fugitive slave act. He was particularly vocal during the Congressional debates over the fate of slavery in Kansas, and strenuously denounced Representative Preston Brooks for his vicious caning of Senator Charles Sumner on the floor of the Senate. Challenged to a duel by Brooks, Wilson declined on legal and moral grounds.

In 1860 Wilson campaigned for Abraham Lincoln's presidential bid, then delivered a hard-hitting condemnation of the Crittenden Compromise during the secession crisis. When the Civil War began, Wilson worked diligently as chair of the Senate Committee on Military Affairs to craft legislation necessary for building and sustaining the Union war effort. He was also an effective recruiter of volunteers in Massachusetts. From the beginning, he encouraged Lincoln toward emancipation and tailored bills which expanded freedom. After the war, Wilson was a strong opponent of President Andrew Johnson's Reconstruction policy and generally sided with the Radical Republicans in Congress, although moderating his opinion as time wore on.

In 1872, the Republican National Convention nominated Wilson to be Grant's vice president, replacing Schuyler Colfax. Wilson was implicated in the Credit Mobilier scandal, but was not censured by Congress. He suffered a stroke in 1873 but had almost fully recovered when he suffered another in November 1875 while presiding over the Senate as vice president. Wilson died twelve days later of a third stroke and was buried in Natick, Massachusetts. He was the author of several books: History of the Antislavery Measures of the Thirty-seventh and Thirty-eighth United States Congresses (1864); Military Measures of the United States Congress, 1861-1865 (1866); History of the Reconstruction Measures of the Thirty-ninth and Fortieth Congresses (1868); and History of the Rise and Fall of the Slave Power in America (3 vols., 1872-77).

Sources consulted: Dictionary of American Biography; William A. DeGregorio, The Complete Book of U.S. Presidents; Harper's Encyclopedia of United States History.