The House Behind the Cedars revolves around the fates of two siblings, John and Rena. As a girl, their mother, Molly Walden, is picked out by a wealthy white man in the town of Patesville on account of her unusual beauty (Molly is African American with light skin and stereotypically white features). This unnamed man takes Molly as his concubine, installs her in the titular house behind the cedars, and fathers John and Rena.

When John is fifteen, he sets out to become a lawyer and pass as white. With the help of Judge Straight, John secretly studies the law. When he is eighteen, he leaves for South Carolina where his parentage is unknown. Ten years later, he returns to Patesville having successfully integrated into the elite white society of Clarence, South Carolina where he owns a large estate and is a successful lawyer. He has come to bring Rena back with him.

After a year at boarding school, Rena makes her social debut in Clarence at a mock chivalric tournament. She catches the eye of George Tryon, a wealthy young lawyer and close friend of John. After a short courtship, George proposes, and Rena accepts.

Rena begins to feel guilty about not telling George the truth of her past and, at the same, begins having troubling dreams about her mother. When a letter comes telling her that their mother is sick, she rushes back to Patesville. Separately, George decides to go to Patesville on business. There, he discovers her secret and breaks off their engagement.

Rena is psychologically crushed and refuses to return to Clarence. She feels a new sense of solidarity with other black people and decides to commit herself to their uplift. Jeff Wain, a supposedly prosperous mixed-race man from Sampson County, visits Patesville and tells people that the local school for black children needs a teacher. Rena soon departs with Wain for Sampson County.

George struggles to put Rena out of his mind. He lives just over the Sampson County line and, late in the school term, hears of Rena’s presence. He asks to meet with her, but she refuses. In the meanwhile, Jeff Wain has turned out to be a villainous figure who has lied about his circumstances and driven his wife away by abusing her. He aggressively pursues Rena.

One day she is caught on a path in the woods between Wain and Tryon. Not wanting to see either man, she flees into the wilderness where she gets lost in the rain. She is found and put to bed but runs away for Patesville. She is found again off the road by her former neighbor Frank Fowler who brings her home. She dies just as George approaches the house to propose again.