Clotel is the sixteen-year-old daughter of the enslaved housekeeper Currer and Thomas Jefferson. Raised in comparative luxury by her mother, she possesses poise, intelligence, and a fair complexion. Her striking beauty attracts the attention of Horatio Green, a wealthy young man who promises to purchase her from the auction block and establish a life together. She holds a deep devotion to her family and a strong Christian faith.

Currer is a biracial woman who formerly worked as a housekeeper for Thomas Jefferson, with whom she had two daughters. Resourceful and protective, she uses the money earned as a laundress to raise her daughters as ladies in Richmond, even hiring a freedman to teach them to read. Upon the death of her master, she faces the auction block and the terrifying prospect of separation from her children.

At fourteen years old, Althesa is the younger sister of Clotel. She shares her family's fair complexion and refined upbringing. Following the auction, a slave speculator separates her from her family and transports her toward the New Orleans market, placing her in a frightening new reality.

Reverend John Peck is a former Connecticut resident who now oversees a congregation and a plantation with seventy slaves in Mississippi. He wields his position as a clergyman to enforce obedience among his slaves, believing the Bible entirely justifies human bondage. He values his public image as a benevolent, pious master while ignoring the actual suffering of the people he owns.

Horatio is a wealthy young white man who purchases Clotel to save her from the general auction. He establishes a secluded cottage near Richmond where they live together outside the bounds of legal marriage. Despite his genuine initial affection, his growing political ambitions and the societal pressures of Virginia begin to challenge his moral fortitude.

The nineteen-year-old daughter of Mr. Peck, Georgiana recently returned to the South after finishing her education in New England. She harbors deep sympathies for the enslaved and firmly believes that slavery contradicts true Christian teachings. She possesses a modest, winning demeanor that she uses strategically to voice her dissenting opinions to her father without crossing the boundaries of nineteenth-century propriety.

Carlton is a Northern free-thinker and skeptic who views organized religion with indifference. Over thirty years old, he relies on his own conscience rather than the Bible. His extended stay at the Peck plantation opens his eyes to the harsh realities of slavery and brings him closer to Georgiana, whose passionate defense of human rights begins to change his worldview.

A young doctor from Vermont, Henry holds strong anti-slavery principles. He is shocked to find a girl as fair as Althesa serving as a chattel slave in his friend's household. He establishes a medical practice in New Orleans while refusing to compromise his beliefs about human liberty, openly condemning the institution of slavery at social gatherings.

Mary is the daughter of Clotel and Horatio Green. Growing up in a secluded cottage, she inherits her mother's striking beauty. Her fair skin draws attention and complicates her existence in a society heavily defined by racial boundaries, placing her at risk when the stability of her parents' relationship falters.

George is an enslaved man in Horatio Green's possession. The son of an American statesman, his skin is light enough that he is often mistaken for a white man. He harbors a fierce desire for freedom and forms a close romantic bond with Mary.

Walker is a slave speculator who transports purchased people to the New Orleans market. He operates with cold efficiency, intentionally separating families early in the morning to avoid emotional scenes that might delay his journey.

Snyder is a missionary retained by slave owners to deliver religious instruction to their slaves. Originally from the North, he stays in the South primarily for Mr. Peck's benefit. He uses scripture intentionally to enforce obedience and compliance among the enslaved population, ensuring they serve their earthly masters.

Sam is considered a prominent slave on Mr. Peck's plantation. Having learned to read in Kentucky, he commands respect from his peers. He previously served as an assistant to a doctor and maintains a proud, carefully managed public persona to navigate his enslaved status.

Gertrude is a wealthy white woman who attracts Horatio's attention as his political ambitions grow. She provides him with social and political advantages, becoming a complication for Clotel's isolated household.

William is an enslaved man who works in Vicksburg, carefully saving money to eventually purchase his freedom. He forms a secretive alliance with Clotel to assist in her escape.

Ellen is one of the daughters born to Henry and Althesa. She is raised in comfort and sent to the North for her education, completely unaware of the Southern laws governing her mother's legal status as a slave.

Jane is the second daughter of Henry and Althesa. Like her sister, she enjoys a refined upbringing and a Northern education, insulated from the harsh realities of Southern race laws.