The novel tells the story of a teenaged runaway referred to only as "the kid", who was born in Tennessee during the famously active Leonids meteor shower of 1833. He first meets the enormous, pale, hairless Judge Holden at a religious revival in a tent in Nacogdoches, Texas, at which Holden falsely accuses the preacher of raping children and goats, inciting the audience to attack him.
After a violent encounter with a bartender that establishes the kid as a formidable fighter, he joins a party of ill-equipped U.S. Army irregulars on a filibustering mission led by a Captain White. White's group is overwhelmed by a Comanche raiding party, and few of them survive. Arrested as a filibuster in Chihuahua, the kid is set free when his acquaintance Toadvine tells the authorities they will make useful Indian hunters. They join John Joel Glanton and his gang, among them Holden, and the bulk of the novel is devoted to detailing their activities and conversations. Though originally tasked with protecting locals from marauding Apaches, the gang devolves into the outright murder of unthreatening Indians, unprotected Mexican villages, and eventually even Mexican soldiers and anyone else who crosses their path, collecting the scalps of Indians to turn in for money whilst looting and massacring the Mexican forces.
According to the kid's new companion Ben Tobin, an "ex-priest", the Glanton gang first met Judge Holden while fleeing for their lives from a much larger Apache group. In the middle of a blasted desert, they found Holden sitting on an enormous boulder, where he seemingly was waiting for and expecting the gang. They agreed to follow his leadership, and he took them to an extinct volcano where he instructed them on how to manufacture gunpowder with the available resources, enough to give them the advantage against the Apaches. When the kid remembers seeing Holden in Nacogdoches, Tobin tells the kid that each man in the gang claims to have met the judge at some point before joining the Glanton gang.
After months of marauding and scalp hunting, the gang crosses into the Mexican Cession, where they eventually set up a systematic and brutal robbing operation at a ferry on the Colorado River at Yuma, Arizona. Local Yuma (Quechan) Indians are at first approached to help the gang wrest control of the ferry from its original owners, but Glanton's gang betrays and slaughters them and the passengers so they can plunder the ferry and frame the Indians for the attack. After a while, the Yumas vengefully attack and kill most of the gang in a second wave. The kid, Toadvine, and Tobin are among the survivors who flee into the desert, though the kid takes an arrow in the leg. The kid and Tobin head west, and come across Holden, who first negotiates, then threatens them for their gun and possessions. Holden shoots Tobin in the neck, and the wounded pair hide among bones by a desert creek. Tobin repeatedly urges the kid to fire upon Holden. The kid does so, but misses his mark.
The survivors continue their travels, ending up in San Diego, California. The kid is separated from Tobin and is subsequently imprisoned. Holden visits the kid in jail, and tells him that he has told the jailers "the truth": that the kid alone was responsible for the end of the Glanton gang. The kid is released on recognizance and seeks a doctor to treat his wound. While recovering from the effects of anesthesia, he hallucinates a visit from Holden along with a curious man who forges coins, and learns what Holden is judge of, and that "the night does not end". The kid recovers and seeks out Tobin, with no luck. He makes his way to Los Angeles, where Toadvine and another member of the Glanton gang, David Brown, were hanged for their crimes.
In 1878, the kid, now in his mid-40s and referred to as "the man", makes his way to Fort Griffin, Texas. At a saloon he meets Holden, who seems not to have aged in the intervening years. Holden calls the man "the last of the true", and the pair talk. Holden declares that the man has arrived at the saloon for "the dance" – the dance of violence, war, and bloodshed that the judge had so often praised. The man disputes Holden's ideas and, noting the performing bear at the saloon, states that "even a dumb animal can dance". When the man goes to an outhouse under another meteor shower shortly afterwards, he runs into the naked Holden, who holds him to his chest and shuts the door. Later, two men open the door to the outhouse and gaze in awe and horror at what they see. The last paragraph finds the judge back in the saloon, dancing and playing the fiddle, saying that he never sleeps and will never die.
In the epilogue, a man is augering lines of holes across the prairie, perhaps for fence posts. The man sparks a fire in each of the holes, and an assortment of wanderers trails behind him.
