Uncle Tom, the title character, was initially seen as a noble, long-suffering Christian slave. In more recent years, however, his name has become an epithet directed towards African-Americans who are accused of selling out to whites. Stowe intended Tom to be a "noble hero" and praiseworthy person. Throughout the book, far from allowing himself to be exploited, Tom stands up for his beliefs and is grudgingly admired even by his enemies.
Eliza is a slave and personal maid to Mrs. Shelby who escapes to the North with her five-year-old son Harry after he is sold to Mr. Haley. Her husband, George, eventually finds Eliza and Harry in Ohio and emigrates with them to Canada, then France and finally Liberia.
The character Eliza was inspired by an account given at Lane Theological Seminary in Cincinnati by John Rankin to Stowe's husband Calvin, a professor at the school. According to Rankin, in February 1838 a young slave woman, Eliza Harris, had escaped across the frozen Ohio River to the town of Ripley with her child in her arms and stayed at his house on her way further north.
Evangeline St. Clare is the daughter of Augustine St. Clare. Eva enters the narrative when Uncle Tom is traveling via steamship to New Orleans to be sold, and he rescues the five- or six-year-old girl from drowning. Eva begs her father to buy Tom, and he becomes the head coachman at the St. Clare house. He spends most of his time with the angelic Eva. Eva often talks about love and forgiveness, even convincing the dour slave girl Topsy that she deserves love. She even touches the heart of her Aunt Ophelia.
Eventually Eva falls terminally ill. Before dying, she gives a lock of her hair to each of the slaves, telling them that they must become Christians so that they may see each other in Heaven. On her deathbed, she convinces her father to free Tom, but because of circumstances the promise never materializes.
A similar character, also named Little Eva, later appeared in the children's novel Little Eva: The Flower of the South by Philip J. Cozans (although this ironically was an anti-Tom novel).
Simon Legree is a cruel slave owner—a Northerner by birth—whose name has become synonymous with greed. He is arguably the novel's main antagonist. His goal is to demoralize Tom and break him of his religious faith; he eventually orders Tom whipped to death out of frustration for his slave's unbreakable belief in God. The novel reveals that, as a young man, he had abandoned his sickly mother for a life at sea and ignored her letter to see her one last time at her deathbed. He sexually exploits Cassy, who despises him, and later sets his designs on Emmeline.
It is unclear if Legree is based on any actual individuals. Reports surfaced after the 1870s that Stowe had in mind a wealthy cotton and sugar plantation owner named Meredith Calhoun, who settled on the Red River north of Alexandria, Louisiana. Generally, however, the personal characteristics of Calhoun ("highly educated and refined") do not match the uncouthness and brutality of Legree. Calhoun even edited his own newspaper, published in Colfax (originally "Calhoun's Landing"), which was renamed The National Democrat after Calhoun's death. However, Calhoun's overseers may have been in line with the hated Legree's methods and motivations.