Morrison's protagonist, Macon "Milkman" Dead III, derives his nickname from the fact that he was breastfed during childhood (Macon's age can be inferred as he was wearing pants with elastic instead of a diaper, and that he later forgets the event, suggesting he was still rather young). Milkman's father's employee, Freddie, happens to see him through the window being breastfed by his mother. He quickly gains a reputation for being a "Momma's boy" in direct contrast to his (future) best friend, Guitar, who is motherless and fatherless.
Milkman has two sisters, "First Corinthians" and "Magdalene called Lena." The daughters of the family are named by putting a pin in the Bible, while the eldest son is named after his father. The first Macon Dead's name was the result of an administrative error when Milkman's grandfather had to register subsequent to the end of slavery.
Milkman's mother (Ruth Foster Dead) is the daughter of the town's only black doctor; she makes her husband feel inadequate, and it is clear she idolized her father, Doctor Foster, to the point of obsession. After her father dies, her husband claims to have found her in bed with the dead body, sucking his fingers. Ruth later tells Milkman that she was kneeling at her father's bedside kissing the only part of him that remained unaffected by the illness from which he died. These conflicting stories expose the problems between his parents and show Milkman that "truth" is difficult or impossible to obtain. Macon is often violently aggressive towards Ruth because he believes that she was involved sexually with her father and loved her father more than her own husband. On one occasion, Milkman punches his father after he strikes Ruth, exposing the growing rift between father and son.
In contrast, Macon Dead Jr.'s sister, Pilate, is seen as nurturing—an Earth Mother character. Born without a navel, she is a somewhat mystical character. It is strongly implied that she is Divine—a female Christ—in spite of her name. Macon (Jr.) has not spoken to his sister for years and does not think highly of her. She, like Macon, has had to fend for herself from an early age after their father's murder, but she has dealt with her past in a different way than Macon, who has embraced money as the way to show his love for his father. Pilate has a daughter, Reba, and a granddaughter named Hagar. Hagar falls desperately and obsessively in love with Milkman, and is unable to cope with his rejection, attempting to kill him at least six times.
Hagar is not the only character who attempts to kill Milkman. Guitar, Milkman's erstwhile best friend, tries to kill Milkman more than once after incorrectly suspecting that Milkman has cheated him out of hidden gold, a fortune he planned to use to help his Seven Days group fund their revenge killings in response to killings of blacks.
Searching for the gold near the old family farm in Pennsylvania, Milkman stops at the rotting Butler Mansion, former home of the people who killed his ancestor to claim the farm. Here he meets Circe, an almost supernaturally old ex-slave of the Butlers. She tells Milkman of his family history and this leads him to the town of Shalimar. There he learns his great-grandfather Solomon was said to have escaped slavery by flying back to Africa, leaving behind twenty-one children and his wife Ryna, who goes crazy with loss. Returning home, he learns that Hagar has died of a broken heart. He accompanies Pilate back to Shalimar, where she is accidentally shot and killed by Guitar, who had intended to kill Milkman.
At the end of the novel, Milkman leaps towards Guitar. This leap is ambiguous, it is not explicitly stated that either or both are killed. However it brings the novel full circle from the suicidal "flight" of Robert Smith, the insurance agent, to Milkman's "flight" in which he learns to fly like Pilate.