Andrew Hawkins, who lives the first two decades of his life as a slave, is the product of the rape of the plantation's mistress by George, the butler in her home. This assault was ordered, however, as a twisted prank by her husband, Jonathan, who himself attempts unsuccessfully to rape George's wife, Mattie.

Amazingly, George and Mattie are not sold away, but George is demoted from house servant to field hand, and he and Mattie raise the baby born after this assault. Jonathan's careless cruelty turns their lives upside down:

Mattie . . . never forgave George, who never forgave Jonathan, who blamed Anna . . . and she demanded a divorce but settled . . . on living in a separate wing in the house. George, who looked astonished for the rest of his life, even when sleeping, was sent to work in the fields. This Fall, he decided, was the wages of false pride . . . It was God's will. He had been a traitor. A tool. He refused Jonathan's apologies and joked bleakly of shooting him or . . . even more bleakly, of spiritual and physical bondage, arguing his beliefs loudly, if ineffectively, on the ridiculously tangled subject Race.

After Andrew leaves the plantation, he goes to work on a farm where the widowed mistress, Flo, is rumored to use the young black male slaves as casual sexual partners (that she soon discards or kills).

Andrew's limited experience with women—his birth mother, his stepmother who raised him, and Flo—convinces him that women are in some ways more essential in life where men are largely superfluous. Reproduction and nurturing are two reasons he identifies women as the abstraction of Being:

[M]en, not Man in the abstract, . . . were inessential, and in the deepest violation of everything we valued in Woman. . . . She did not need us for satisfaction, or even reproduction—there were parthenogenones. . . . [Man] was the freak who fell back on thought in the absence of feeling, created history because he could not live Being's timeless cycles. . . . [T]he sexual war was a small skirmish—a proxy war, with women as the shock troops for a power that waited, mocking the thoroughly male anxiety for progress.

Andrew, in collaboration with another slave named Reb, escapes Flo's clutches, but his ambivalent attitude toward gender stays with him. Only the "ridiculously tangled subject" that is race causes him more analytical and experiential problems.

Andrew's adventures place him, as a protagonist, in the picaresque tradition, even as Johnson draws on traditional American slave narratives to construct a tale of a journey out of bondage. While Andrew's initial dream is to work, earn money, and buy his freedom, he comes to realize the insoluble paradox involved therein: if it is freedom, it cannot be bought.

When Andrew escapes Leviathan and eludes the grasp of Hank, an evil slave-hunter, Reb explains why Hank will never catch him:

How the Hell you gonna catch a Negro like that? He can't be caught. He already free. . . . You got to have something static or dead inside you—an image of yoself—fo a real slave-catcher to latch onto

A final twist comes when Andrew, who is feigning freedom by passing as white, attempts to liberate Minty, a woman he had loved and hoped to free; he does so by buying her, in the guise of white slave owner. The reader is left to determine if this means that Andrew retains something "dead inside" him.