In 1833, a wild, imposing man named Thomas Sutpen comes to Jefferson, Mississippi, with a group of slaves and a French architect in tow. He buys a hundred square miles of land from an Indian tribe, raises a manor house, plants cotton, and marries the daughter of a local merchant, and within a few years is entrenched among the local aristocracy. Sutpen has a son and a daughter, Henry and Judith, who grow up in a life of uncultivated ease in the northern Mississippi countryside. Henry goes to college at the University of Mississippi in 1859, and meets a sophisticated fellow student named Charles Bon, whom he befriends and brings home for Christmas. Charles meets Judith, and over time, an engagement between them is assumed. But Sutpen realizes that Bon is actually his own son—Henry and Judith's half-brother—from a previous marriage which he abandoned when he discovered that his wife had Black blood. He tells Henry that the engagement cannot be, and that Bon is Henry's own brother; Henry reacts with outrage, refusing to believe that Bon knew all along and willingly became engaged to his own sister. Henry repudiates his birthright, and he and Bon flee to New Orleans. When war breaks out, they enlist, and spend four hard years fighting for the Confederacy as the South crumbles around them. At the end of the war, Sutpen (a colonel) finds his son and reveals to him that not only is Bon his and Judith's half-brother, he is also, in part, a Black man.

That knowledge makes Henry revolt against Bon in a way that even the idea of incest did not, and on the day Bon arrives to marry Judith, Henry murders him in front of the gates of the Sutpen plantation. Sutpen returns to a broken house, and becomes a broken—though still forceful—man; he slides slowly into alcoholism, begins an affair with a fifteen-year-old white girl named Milly, and continues in that vein until, following the birth of his and Milly's daughter, he is murdered by Milly's grandfather Wash Jones in 1869.

Decades later, in 1909, Quentin Compson is a twenty-year-old man, the grandson of Sutpen's first friend in the country (General Compson), who is preparing to leave Jefferson to attend Harvard. He is summoned by Miss Rosa Coldfield, the sister of Sutpen's wife Ellen (and briefly Sutpen's fiancee herself), to hear the story of how Sutpen destroyed her family and his own. Over the following weeks and months, Quentin is drawn deeper and deeper into the Sutpen story, discussing it with his father, thinking about it, and later telling it in detail to his Harvard roommate Shreve. The story is burned into his brain the night he goes with Miss Rosa to the Sutpen plantation, where they find Henry Sutpen— now an old man—waiting to die. Months later, Rosa attempts to return for Henry with an ambulance, but Clytie, Thomas Sutpen's daughter with a slave woman and now a withered old woman herself, sets fire to the manor house, killing herself and Henry, and bringing the Sutpen dynasty to a fiery end.

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