Uncle Tom's Cabin is dominated by a single theme: the evil and immorality of slavery. While Stowe weaves other subthemes throughout her text, such as the moral authority of motherhood and the redeeming possibilities offered by Christianity, she emphasizes the connections between these and the horrors of slavery. Stowe sometimes changed the story's voice so she could give a "homily" on the destructive nature of slavery (such as when a white woman on the steamboat carrying Tom further south states, "The most dreadful part of slavery, to my mind, is its outrages of feelings and affections—the separating of families, for example."). One way Stowe showed the evil of slavery was how this "peculiar institution" forcibly separated families from each other.
Because Stowe saw motherhood as the "ethical and structural model for all of American life" and also believed that only women had the moral authority to save the United States from the demon of slavery, another major theme of Uncle Tom's Cabin is the moral power and sanctity of women. Through characters like Eliza, who escapes from slavery to save her young son (and eventually reunites her entire family), or Eva, who is seen as the "ideal Christian", Stowe shows how she believed women could save those around them from even the worst injustices. While later critics have noted that Stowe's female characters are often domestic clichés instead of realistic women, Stowe's novel "reaffirmed the importance of women's influence" and helped pave the way for the women's rights movement in the following decades.
Stowe's puritanical religious beliefs show up in the novel's final, overarching theme—the exploration of the nature of Christianity and how she feels Christian theology is fundamentally incompatible with slavery. This theme is most evident when Tom urges St. Clare to "look away to Jesus" after the death of St. Clare's beloved daughter Eva. After Tom dies, George Shelby eulogizes Tom by saying, "What a thing it is to be a Christian." Because Christian themes play such a large role in Uncle Tom's Cabin—and because of Stowe's frequent use of direct authorial interjections on religion and faith—the novel often takes the "form of a sermon."