Requiem for a Nun is the sequel to William Faulkner's bestselling novel Sanctuary. It centers on the character of Temple Drake eight years after her harrowing kidnapping ordeal by the gangster, Popeye, where she was forced to live in a brothel and then later lied in court to defend him. The book switches between prose and play form, often launching into the dense, long-winded descriptions and meandering character thoughts that Faulkner was famous for.

In Requiem, Temple is married to Gowan Stevens, her alcoholic comrade from Sanctuary, and the mother of two children—a young son and an infant daughter. Despite an outwardly stable appearance and their status in polite society, their marriage is rocky because of Temple's fond attachment to her past life in the brothel.

At the outset of the book, the children's nursemaid, Nancy, a former whore and drug addict that Temple took in, is being accused of murdering the infant daughter in her crib, and as a result will be hanged. However, just before the execution, Temple comes to the conclusion that she herself is responsible for the death of her baby stemming from her own actions eight years earlier.

After drugging Gowan with a sleeping pill, she secretly confesses to Gowan's uncle, Gavin, who happens to be Nancy's defense attorney, why she feels Nancy should be spared. Gavin pleads with her to appeal directly to the governor of Mississippi in order to stop the execution. Gowan, meanwhile, has woken up and overheard the entire conversation without Temple realizing it.

The day before the hanging, Temple goes to the governor's office and confesses that she was going to leave her family and run away with another man. Nancy smothered the baby in a misguided attempt to stop her from leaving. Unbeknownst to Temple, however, the governor has already denied clemency for Nancy and it turns out to be Gowan sitting in the governor's chair, listening and learning everything.

In the end, Temple and Gavin are unable to stop Nancy execution, but they go visit her and make amends. Nancy knows she must die for her actions and Temple must live with the consequences of hers. The story is meant to extol the virtue of suffering and we leave Temple tormented, realizing that this will forever be her lot in life.