As a slave, Clotel, like Laïsa and Georges's wife, Zelia, has no rights, no choice regarding how she is treated, where she will live, or what will happen to her. Although her white master Horatio Green seems fond of Clotel, making her his mistress, and moving her to an apparently idyllic space in Virginia, and although the couple has a daughter during their relationship, Green, who marries a wealthy white woman from a prominent family, succumbs to his wife's jealousy and his father-in-law's demands that he sell Clotel.

In placing his social and political aspirations above the love he may feel for Clotel, Green acts expediently, allowing his father-in-law to sell his slave mistress.

Her sale forces her from her former refuge and separates her from her beloved daughter. Clotel’s tenuous security continues to be threatened, as she is sold two additional times.

Her second new master attempts to seduce her with "glittering presents" and the likelihood of ensuing rape should she resist. Like Zelia in "The Mulatto," Clotel rebels against the space in which her humanity remains in jeopardy. Facing sexual exploitation, Clotel flees. In Chapter XIX, Clotel's rebellion becomes a successful, albeit momentary, escape in which, although ably impersonating a white invalid gentleman, she gives in to her maternal instincts.

She forgoes her autonomy by returning to Virginia, intending to reunite with her daughter. Clotel has returned to a space where she is regarded as property, without control over how she will be used. While Clotel's escape—her rebellion against her master— has been skillfully executed, she feels that she cannot live a life of freedom in a place removed from her dear daughter. Her rebellion, if she continued to pursue her freedom, then, would become the equivalent of her family's destruction.

Zelia succumbs to the systemic structure of slavery that makes rebellion against the master the equivalent of self-immolation. In contrast, Clotel temporarily escapes this fate by rejecting her freedom and returning to Virginia in hopes of a mother and child reunion. Clotel risks re-enslavement, a return to oppressive conditions in place where, if recaptured, she will be forced back into bondage. Yet Clotel's actions do not bring about reunion.

Recaptured and incarcerated in the District of Columbia — the seat of national government symbolizing the liberties that slaves are denied — Clotel confronts her imminent sale in the New Orleans market. There, she will likely be sexually exploited and never see her daughter again. Her rebellion suppressed, Clotel escapes once more, but when faced with recapture, chooses to jump to her death off a Potomac bridge.