In 1980, hitman Anton Chigurh is arrested in Texas. He escapes by strangling the sheriff's deputy and steals a car by killing the driver with a captive bolt pistol. Meanwhile, Llewelyn Moss is hunting pronghorns in the desert. He comes across the aftermath of a drug deal gone wrong, finding several dead men, a wounded Mexican man begging for water, drugs in a truck, and a briefcase containing $2 million in cash. He takes the briefcase and returns home. Feeling guilty, he returns with water that night but finds the man has died. He looks up to the ridge and sees two men with guns who pursue him in a truck. He escapes into a river, shooting the men's dog as it chases him.
Chigurh spares the life of a gas station owner for correctly calling a coin toss and is later hired to recover the money. After making his way back home, Moss sends his wife, Carla Jean, to stay with her mother. Terrell County Sheriff Ed Tom Bell begins investigating the failed drug deal. Chigurh searches Moss's trailer home, using his bolt pistol to blow out the door lock. Moss takes a taxi to a motel in Del Rio, where he hides the briefcase in his room's air duct. Following a tracking device hidden in the case, Chigurh goes to Moss' motel and kills a group of Mexicans. Moss has rented a second room adjacent to the Mexicans' room with access to the duct where the money is hidden. He retrieves the briefcase before Chigurh opens the duct.
Moving to a hotel in the border town of Eagle Pass, Moss discovers the tracking device, but Chigurh has already found him. Their firefight spills onto the streets, killing a truck driver and heavily wounding both. Moss flees to Mexico, hiding the case along the Rio Grande. A norteño band takes Moss to a hospital. Chigurh cleans and stitches his wounds with stolen supplies. Carson Wells, a bounty hunter, offers Moss protection in exchange for the money, but he refuses. Chigurh ambushes Wells at his hotel. The phone rings as Wells is bartering for his life. Chigurh shoots him and takes the call from Moss, vowing to kill Carla Jean unless Moss gives up the money.
Moss retrieves the case from the Rio Grande and arranges to meet Carla Jean at a motel in El Paso, where he plans to give her the money and hide her from danger. Carla Jean's mother unknowingly reveals Moss' location to a group of Mexicans tailing them. Bell reaches the motel in El Paso, only to find that the Mexicans have killed Moss. Carla Jean arrives later and bursts into tears when Bell somberly removes his hat.
That night, Bell returns to the crime scene and observes the lock blown out. Bell thinks that Chigurh is hiding, but when Bell hesitantly enters, he finds the room empty. Later, Bell visits a man called Ellis and tells him he plans to retire because he feels overmatched by the recent violence. Ellis tells Bell of a story in which a lawman, Ellis' uncle, was killed on his porch and says that the region has always been violent.
Carla Jean returns from her mother's funeral to find Chigurh waiting in the bedroom. She refuses his offer of a coin toss for her life. Chigurh checks the soles of his boots as he leaves the house. As he drives through the neighborhood, another car crashes into him, breaking his arm. He bribes two boys for a shirt to use as a sling and flees on foot.
Now retired, Bell shares two dreams with his wife. In the first, he lost some money his father had given him. In the other, as he rode through a snowy mountain pass, his father rode past him to prepare a campfire ahead.
