Arthur Shelby, a successful farm owner and business mas, has found himself in deep debt. Despite the excellent relationship he has with his slaves, begrudgingly, he decides to sell Uncle Tom, a middle-aged man with family on the farm, and Harry, the young son of Mrs. Shelby's maid Eliza, to an evil, heartless slave trader- Mr. Haley. Eliza hears of the plot, and immediately flees with Harry to the North, hoping for freedom in Canada with her husband, George. Mr. Haley hires a slave hit-man, Loker, to retrieve Eliza and Harry, but with the help from some Quakers, the family is reunited with George, and continues on their journey to Canada together.


Meanwhile, Uncle Tom leaves his family and home, and is transported by Mr. Haley to a slave market by boat. While on board, he befriends a young white girl, Eva, and upon rescuing her from falling into the river, is bought by Eva's kindly father, Augustine St. Clare. Uncle Tom returns to the St. Clare's home in New Orleans, where he grows increasingly closer to Eva, who shares in his strong Christian faith. Up North, Eliza and her family are found by Loker, who attempts to capture them, but is shot in the side by George. Loker is brought to a Quaker settlement to be healed. After two years with the St. Clares, Eva becomes very ill and soon dies. Her death sets off a string of tragic events, and soon St. Clare is stabbed to death, but in his death he finds God and is reunited with his mother and daughter in heaven.


In great bitterness, St. Clare's evil wife sells Uncle Tom to a demented plantation owner named Simon Legree. Among a group of new slaves, including a young girl, Emmeline, who the demonic Legree intends to use as a sex slave, Uncle Tom is transported to his new master's rural Louisiana plantation. Legree soon finds a deep hatred for Uncle Tom after he refuses to beat a fellow slave, and determines to shake Uncle Tom from his Christian faith. Loker- now a changer man, assists Eliza, Harry, and George across the border to Canada and liberation from slavery. In Louisiana, Tom's faith is nearly shattered by Legree, but he overcomes it when he has two visions, one of Jesus Christ and one of Eva, which give him the spiritual strength to persevere through Legree's torment. Uncle Tom helps his masters two sex slaves, Cassie and Emmeline to escape, and when he refuses to expose their whereabouts, is beaten within an inch of his life by Legree. Immediately after that George Shelby arrives, with the money in hand to free Uncle Tom, but he is too late; all he can do is watch, as Uncle Tom struggles and dies- a martyr.


Cassy and Emmeline travel to Canada, on the way meeting George's sister who goes with them. Upon arrival, Cassy realizes that Eliza is her long lost daughter, and the whole family leaves for Liberia, an African nation that was created as a haven for former American slaves. George Shelby returns home to his farm, where he sets all of his slaves free in honor of Tom, and he urges them to remember him when they look at his cabin, and live a life honoring to God, even to death, like Tom.