Go Down, Moses is a collection of short stories (and two longer stories, "The Fire and the Hearth" and "The Bear") that, together, tell the composite history of the McCaslin family, of the descendents of Carothers McCaslin and the residents of the plantation he founded. The complete histories emerge gradually over the course of the book, with bits of information appearing in successive stories to clarify, complete, and sometimes controvert the information given in previous stories. But each story has its own plot, as well, independent of the other stories. The stories are:

"Was," in which young McCaslin Edmonds helps his Uncle Buck chase the slave Turl to Hubert Beauchamp's plantation, where Buck narrowly avoids having to marry Beauchamp's sister Sophonsiba, and returns with Tennie, a slave for Turl to marry--which will stop him from escaping so often.

"The Fire and the Hearth," in which Lucas Beauchamp, Carothers McCaslin's grandson descended from a negro lover, searches for buried treasure on the McCaslin plantation, only to be thwarted by his wife's decision to divorce him.

"The Pantaloon in Black," in which a big negro named Rider struggles with grief over his wife Mannie's early death and ends up killing a white man and getting lynched in retribution.

"The Old People," in which a young boy named Isaac McCaslin, under the tutelage of his part-Indian mentor Sam Fathers, kills his first buck, is anointed in its blood, and sees a giant, almost mystical buck that Sam refers to as "grandfather."

"The Bear," in which Isaac McCaslin becomes a master hunter and, with the group of older hunters at Major de Spain's camp, tracks Old Ben, a giant bear; later, his experiences cause him to repudiate his birthright and refuse the inheritance of the McCaslin plantation, out of a belief that no man can own the land.

"Delta Autumn," in which Isaac McCaslin, now an old man, goes on a final hunting trip to the Mississippi River Delta, where he meets a young woman who has had Carothers Edmonds's child.

"Go Down, Moses," in which Gavin Stevens, the Jefferson district attorney, helps Molly Beauchamp acquire the body of her executed grandson.