The novel concerns a returning World War II veteran who, haunted by a life-long crisis of faith, resolves to form an anti-religious ministry in an eccentric, fictionalized city in the Southern United States after finding his family homestead abandoned without a trace.

The novel received little critical attention when it first appeared but has since come to be appreciated as a classic work of "low comedy and high seriousness" with disturbing religious themes.

[3] Recently discharged from service in World War II and surviving on a government pension for unspecified battle wounds, Hazel Motes returns to his family home in Tennessee to find it abandoned.

Despite his aversion to all trappings of Christianity, he constantly contemplates theological issues and finds himself compelled to purchase a hat and suit that cause others to mistake him for a minister.

Emery introduces Motes to the concept of "wise blood," an idea that he has innate, worldly knowledge of what direction to take in life, and requires no spiritual or emotional guidance.

Emery and Motes witness a blind preacher Asa Hawks and his 15-year-old daughter Sabbath Lily crash a street vendor's potato peeler demonstration to advertise for their ministry.

Asa has Sabbath Lily give Motes an old newspaper clipping announcing his intention to blind himself with quicklime at a revival meeting to detach himself from worldly pursuits.

Initially intending to seduce Sabbath Lily in order to corrupt her spiritual purity, Motes discovers that she is in fact interested in him.

Meanwhile, Emery, believing that Motes' church needs a worldly "prophet," breaks into a museum and steals a mummified dwarf, which he begins keeping under his sink.

During an extended period of living as an ascetic at the boarding house, he begins walking around with barbed wire wrapped around his torso and sharp rocks and pebbles in his shoes.

Angry at being asked to return what they believe is a mentally ill indigent, one of the cops who find Motes strikes him in the head with his baton.

In the introduction to the 10th anniversary publication of Wise Blood, O'Connor states that the book is about freedom, free will, life and death, and the inevitability of contention regarding belief and disbelief.

An immersive opera and gallery installation, WISE BLOOD [1], libretto adapted from the novel by Anthony Gatto, was commissioned by Walker Art Center and The Soap Factory[usurped] (Minneapolis, Minnesota USA) in May and June 2015.

From the Soap Factory website: "Visual artist Chris Larson and composer Anthony Gatto join forces to bring the darkly humorous world of Flannery O'Connor's WISE BLOOD to life.

Set in the post-industrial beauty of a 130-year-old factory space turned art gallery, this immersive opera takes the audience on a journey alongside the eccentric and always captivating characters of this story.

[8] Red Label Catharsis named its second album and title track, "Jesus Made it Beautiful To Haunt Her" directly from one specific page in Wiseblood where Sabbath Lily tells Hazel a story about a mother who strangles her baby.