Arthur Shelby, a Kentucky farmer and slaveowner, is forced by debt to sell two slaves — Uncle Tom and Harry, the young son of his wife's servant Eliza — to a trader named Haley. Eliza hears the discussion, warns Tom and his wife, and runs away with her child, followed by Haley, who is prevented from catching her when she crosses the Ohio River and is aided by helpful citizens. Haley meets two slave-catchers who agree to pursue Eliza and Harry. Meanwhile Tom refuses to run away and is taken by Haley toward New Orleans. Before leaving Kentucky, however, Haley buys several more slaves, and one of them (a young mother whose infant Haley sells without her knowledge) commits suicide.
Some time later, Eliza's husband, George Harris, himself an escaped slave in disguise, discovers that Eliza is headed for Canada and sets out to find and join her. Meanwhile, Eliza and her son have been taken in by a Quaker family and are joined by George to prepare for the next stage of their escape.
Tom, on a Mississippi river boat, meets a little white girl named Eva St. Clare, is touched by her beauty and gravity, and rescues her from drowning. Eva's father buys Tom from Haley at Eva's request, and Tom accompanies the family (father, daughter, and cousin Ophelia) to their New Orleans home. There he meets Eva's mother, a spoiled and bigoted woman, and other slaves belonging to the household. He and Eva form a close relationship; by reading to Tom from his Bible, Eva herself grows to understand and love Christianity.
