The plot of the novel follows the experiences and thoughts of three central characters, Sheriff Ed Tom Bell, hunter and Vietnam veteran Llewelyn Moss, and psychopathic hitman Anton Chigurh, tracing how their paths intersect over the course of a series of highly disturbing and violent events.
The novel opens with a monologue from protagonist Sheriff Ed Tom Bell, detailing an experience from his time as a sheriff. He recalls a time when a man who is now being put to death based on Bell’s own testimony killed a 14 year old girl, and though it was described as a ‘crime of passion’ by investigators, he told Bell there was no passion involved. Bell realizes that his worldview is dated, and likely fundamentally different from that of others near the Mexico-US border in 1980. He believes in the idea of an agent of destruction that embodies this mentality, one that a man would have to risk his soul confronting. Bell does not believe himself to be willing to take that risk.
Meanwhile, Llewelyn Moss comes across what appears to be the grisly aftermath of a drug deal gone wrong while out hunting antelope. After searching the area, he comes across a badly wounded Mexican survivor, who pleads with Moss for water, which Moss denies him since he doesn’t have any on him. After investigating further, Moss discovers a truck filled with heroin and decides to go off and look for the “Last Man Standing.” He finds him, dead under a tree some ways away from the scene, clutching a satchel filled will $2.4 million in cash. Moss takes the satchel and returns home to his trailer, but feels significant remorse at having left the thirsty man to die, and returns later that night with a jug of water. Upon arriving, he finds that the man has since been shot and killed, and it’s not long after that that a second truck pulls up beside Moss’s, leading to an intense chase through the desert. This marks the beginning of the hunt for Llewelyn Moss, a conflict that will drive the novel for its majority.
Moss manages to escape, and returns home to tell his wife, Carla Jean, to go to her grandmother's in Odessa, Texas while he escapes with the money. Sheriff Bell is called in to investigate the drug crime and protect Moss and Carla Jean. Bell is haunted by his experiences as a soldier during WWII, where he left his unit to die but received a Bronze Star in the aftermath. Bell has spent his life attempting to atone for that crime of cowardice, and resolves to crack the case and save the Mosses lives in the process. Of course, things are never that simple, and hitman Anton Chigurh soon arrives on the scene. Chigurh was hired to retrieve the money, and with his silenced shotgun and “stungun” (captive bolt pistol) at his side, he hunts Moss and the money will a relentless ferocity. Also hot on the trial is ex-special forces officer and rival hitman Carson Wells, who is familiar with Chigurh and the kind of carnage he can inflict when he sets his mind to it. After a shoot out on the border that leaves both Moss and Chigurh badly wounded, Moss goes to recover in a hospital in Mexico, while Chigurh steals medical supplies to patch himself up.
During his time in the hospital, Moss is approached by Carson Wells, who offers to protect him in exchange for the money. Moss turns him down, but Wells leaves his contact information with him, telling Moss to call him when he feels like he can no longer handle Chigurh alone. When Chigurh recovers from his wounds, he quickly tracks down Wells and murders him shortly before Moss calls to negotiate the exchange of the money. Chigurh answers the phone, and tells Moss that he will kill Carla Jean if he fails to hand over the cash. Moss refuses, and quickly calls Carla Jean to tell her to meet him in a motel in El Paso. Carla Jean deliberates for a while on whether or not to tell Sheriff Bell, but she eventually does and the call is traced by several of the hunters looking for Moss.
When he arrives at the motel, Sheriff Bell finds a massacre. Moss has been murdered by a group of Mexicans prior to his arrival. Chigurh arrives later that night, retrieves the satchel from where Moss hid it in the motel, and returns it to its owner. Later, he travels to Carla Jean's house to settle some unfinished business. He flips a coin to decide her fate, and after shooting her, is struck by a car. Chigurh survives, and after bribing two teenagers to forget they ever saw him, limps down the road, completely eluding the authorities for a clean getaway. It's unclear whether he can survive his injuries from the crash, but authorities never track him down.
After a lengthy but fruitless investigation, Bell relents and retires, leaving the case feeling defeated. Afterward, Bell recalls two dreams: one where he asked to borrow money from his father, and one where they were riding horses through snowy mountains. In the second dream, Bell’s father rides ahead, carrying a white horn filled with fire into the darkness. Bell takes this as a sign that he is an old man now, and the country in which he lives is truly no country for old men.
