Stowe, a Connecticut-born teacher at the Hartford Female Seminary and an active abolitionist, wrote the novel as a response to the passage, in 1850, of the second Fugitive Slave Act. Much of the book was composed in Brunswick, Maine, where her husband, Calvin Ellis Stowe, taught at his alma mater, Bowdoin College.
Stowe was partly inspired to create Uncle Tom's Cabin by the slave narrative The Life of Josiah Henson, Formerly a Slave, Now an Inhabitant of Canada, as Narrated by Himself (1849). Henson, a formerly enslaved black man, had lived and worked on a 3,700-acre (15 km2) tobacco plantation in North Bethesda, Maryland, owned by Isaac Riley. Henson escaped slavery in 1830 by fleeing to the Province of Upper Canada (now Ontario), where he helped other fugitive slaves settle and become self-sufficient, and where he wrote his memoirs. Stowe acknowledged in 1853 that Henson's writings inspired Uncle Tom's Cabin. When Stowe's work became a best-seller, Henson republished his memoirs as The Memoirs of Uncle Tom and traveled on lecture tours extensively in the United States and Europe. Stowe's novel lent its name to Henson's home—Uncle Tom's Cabin Historic Site, near Dresden, Ontario, Canada—which since the 1940s has been a museum. The cabin where Henson lived while he was enslaved no longer exists, but a cabin on the Riley farm erroneously thought to be the Henson Cabin was purchased by the Montgomery County, Maryland, government in 2006. It is now a part of the National Park Service National Underground Railroad Network to Freedom program, and plans are underway to build a museum and interpretive center on the site.
American Slavery As It Is: Testimony of a Thousand Witnesses, a volume co-authored by Theodore Dwight Weld and the Grimké sisters, is also a source of some of the novel's content. Stowe said she based the novel on a number of interviews with people who escaped slavery during the time when she was living in Cincinnati, Ohio, across the Ohio River from Kentucky, a slave state. In Cincinnati the Underground Railroad had local abolitionist sympathizers and was active in efforts to help runaway slaves on their escape route from the South.
Stowe mentioned a number of the inspirations and sources for her novel in A Key to Uncle Tom's Cabin (1853). This non-fiction book was intended to verify Stowe's claims about slavery. However, later research indicated that Stowe did not read many of the book's cited works until after she had published her novel.