When about twelve, she went to Hartford, where her sister Catherine had opened a school. While there she was known as an absent-minded and moody young lady, odd in her manner and habits, but a fine scholar, excelling especially in the writing of compositions. In 1832, her father assumed the presidency of Lane Theological Seminary in Cincinnati, Ohio, she followed her family. On the fifth of January, 1836, she married Professor Calvin E. Stowe, a man of learning and distinction. In Cincinnati, she came into contact with fugitive slaves.

Stowe was catapulted to international fame with the publication of Uncle Tom's Cabin in 1851. . Following publication of the book, she became a celebrity, speaking against slavery both in America and Europe. She wrote A Key to Uncle Tom's Cabin (1853) extensively documenting the realities on which the book was based, to refute critics who tried to argue that it was inauthentic; and published a second anti-slavery novel, Dred in1856.

The following excerpt is taken from the last chapter of Uncle Tom's Cabin, which very much resembles a sermon. She urges white Northerners to welcome escaped slaves and treat them with respect.

Thereafter, Stowe became one of America's best-paid and most famous writers. Born into a distinguished New England family, Stowe began her career writing stories for a Cincinnati literary club. Stowe was fortunate to have begun her career before writing had become sufficiently remunerative in the United States to allow men to dominate the profession. First published in weekly installments from June 5, 1851 to April 1, 1852 in the journal National Era, Stowe's novel created such a controversy that when she was introduced to President Abraham Lincoln in 1862, he is said to have greeted her with the words: "So you are the little woman who wrote the book that started this great war!"