Our protagonist, an unnamed priest, has come to a river port in the hope of escaping a Mexican state government that wants him dead. All because he's a priest, which in this state is a crime of treason! He's the last one, so no pressure or anything.
He doesn't get out. First because he passes the time drinking brandy with an English dentist named Mr. Tench, and second because he grudgingly decides to help a boy's dying mother.
Meanwhile, the lieutenant, our not-so-friendly neighborhood antagonist, asks his chief for the authority to take hostages from the villages the priest visits and shoot them if the villagers don't turn in the traitor cleric. The chief digs it, and the plan is implemented.
On the run again, the priest finds temporary shelter at the home of Captain Fellows and then in a village of people desperate to confess their sins and receive the Eucharist at Mass. He next seeks safety in the village of his daughter and her mother. In the early morning before dawn, the priest says Mass as reports come to him that the police are near and headed his way. When the lieutenant arrives, the villagers refuse to give the priest over to him, and he takes a hostage.
After an awkward moment with his daughter, the priest departs and heads toward Carmen. On the way, an unwelcomed companion called the mestizo (or half-caste) joins him. Sensing the man's coming betrayal, the priest tries several times to ditch him and finally succeeds.
Now in the capital, the priest needs wine so he can continue to say Mass. An opportunity to obtain it turns bitter after the priest is arrested for carrying brandy. In prison he meets the mestizo, staying there as a guest, but the would-be traitor won't turn him in now knowing he'll get no reward. He's a crafty one, that's for sure.
The priest is released from prison and given a little money by the lieutenant. The priest makes for the mountains and the border of the state. Though feverish, he escapes.
Enjoying once again a life of comfort and relative luxury, the priest is none too pleased when the half-caste shows up again, claiming that a man has been shot and needs a priest before he dies. The priest's Spidey-sense detects the trap, but, believing himself duty-bound, he follows his own personal Judas. The man, an American criminal, is indeed dying, but refuses confession. The setting is indeed a trap, and the priest is finally caught.
News that the last priest has been detained reaches the people who had helped him along his way: Captain Fellows and his wife, Mr. Tench, who's trying his best to relieve the chief of police's tooth ache and watches the execution from the window, and a mother who has been reading a prohibited religious book to her children.
In the last scene of the novel, a new priest shows up. He'll have his own joys and sorrows no doubt.