Hazel is a cynical World War II veteran returning home to the South. Raised by a traveling preacher grandfather, Hazel utterly rejects his religious upbringing, actively declaring his atheism to strangers. Despite his fierce denial of faith, he wears his grandfather's distinctive hat, causing locals to frequently mistake him for a clergyman. He purchases a dilapidated Essex car to use as his home and pulpit for a movement he calls the "Church Without Christ."

Enoch is an isolated, erratic young man who works as a guard at the City Forest Park. He is driven by strange, unexplainable bodily instincts he refers to as his "wise blood." Upon encountering Hazel Motes, Enoch becomes entirely obsessed with him, desperately wanting to share a secret relic he guards at the local museum. He frequently trails Hazel around the city despite constant rejection.

Asa is an aging, scarred street preacher who wanders Taulkinham handing out religious tracts. He claims to have blinded himself with quicklime years ago to prove his redemption through Jesus. He becomes the primary target of Hazel's anti-religious obsession, though Asa finds the younger man disturbing and attempts to avoid his aggressive debates.

Sabbath is the teenage daughter of the blind street preacher Asa Hawks. She assists her father in begging and distributing religious tracts around the city streets. Beneath her outwardly pious duties, she is deeply pragmatic and quickly develops a strong, cunning infatuation with Hazel Motes, attempting to flirt with him despite his obvious hostility.

Onnie Jay is a talented orator and street grifter who hears Hazel preaching and immediately sees an opportunity for profit. When Hazel rejects his partnership, Onnie Jay decides to hijack the message entirely, setting up a rival operation called the "Church of Christ Without Christ" and charging people to join.

Mrs. Flood is the landlady of the boarding house where Hazel rents a room. She initially finds his extreme behavior odd but becomes highly interested in his regular government pension checks. Her financial interest gradually morphs into a calculated plan to marry him and secure her own future.

Solace is a man hired by Onnie Jay Holy to act as a "Prophet" for his rival church. He dresses similarly to Hazel Motes to confuse the public and attract crowds, drawing Hazel's deep and violent ire for mocking his genuine anti-religious beliefs.

A large, talkative woman on the train to Taulkinham. She attempts to make polite conversation with Hazel about her family, but is quickly unsettled by his intense and unprompted anti-religious remarks.

A sex worker advertised on a train station bathroom wall as having the "friendliest bed in town." She provides Hazel with a place to stay upon his arrival in Taulkinham and is entirely unfazed by his intense declarations that he is not a preacher.

An older used-car salesman running a lot called "Slade's For the Latest." He recognizes Hazel's desperation for a vehicle and sells him a severely dilapidated, rat-colored Essex for forty dollars.

An employee at a local shop where Enoch and Hazel stop for milkshakes. She takes an instant dislike to Enoch due to his disrespectful behavior but notes that Hazel seems like a "clean boy."