Thurlow Weed was born in Cairo, New York, the son of a poor farmer. He spent his youth working in a print shop and on Hudson River boats, receiving little formal schooling during those years.
Weed saw brief service in the War of 1812 and later became the foreman at the Albany Register. In the 1820s he became active in local and state politics, initially as a supporter of DeWitt Clinton. In 1824 he supported the presidential bid of John Quincy Adams and used his political skills to help engineer Adams electoral victory in New York. In the same year he was elected to the state assembly and later bought the RochesterTelegraph.
Weed was active in the Anti-Masonic movement in New York, opposing the Albany Regency of Martin Van Buren. In 1829 Weed established the Albany Evening Journal and became a strong advocate of Henry Clays American System. In the 1830s the Anti-Masonic movement was absorbed by the Whig Party where Weed continued his activism. He was a sincere opponent of slavery, but on many other issues he would tread carefully to avoid political setbacks. He was noted for being a stern and sometimes ruthless political boss, but always exhibiting an amiable personality.
In 1838 he engineered the gubernatorial bid of William H. Seward, his closest friend and political ally. Later he supported the presidential runs of Whigs William Henry Harrison and Zachary Taylor. The enactment of the Compromise of 1850 and Millard Fillmores presidency convinced Weed that the Whigs were doomed; he traveled abroad and joined the Republican Party after his return.
Weeds greatest political disappointment was his failure to secure the 1860 presidential nomination for his friend Seward. Nevertheless, he was a staunch supporter of Abraham Lincoln after the election, advised the new president on political appointments and served as an unofficial envoy to Britain and France during the war. His opposition to the Emancipation Proclamation led to a loss of influence, and his later support for Andrew Johnsons reconstruction policy ended his political career.