In rural Texas, welder and hunter Llewelyn Moss discovers the remains of several drug runners who have all killed each other in an exchange gone violently wrong. Rather than report the discovery to the police, Moss decides to simply take the two million dollars present for himself. This puts the psychopathic killer, Anton Chigurh, on his trail as he dispassionately murders nearly every rival, bystander and even employer in his pursuit of his quarry and the money. As Moss desperately attempts to keep one step ahead, the blood from this hunt begins to flow behind him with relentlessly growing intensity as Chigurh closes in.

Tired and irritable, Zakes Abbott drives home along the motorway, his girlfriend, Beth, asleep beside him. Failing to spot his exit he speeds across the causeway, cutting up a white van and barely avoiding an accident. Apoplectic with rage, the truck driver gives chase, and as he violently overtakes the tailgate flips up revealing a woman bound and bloodied in the back. But before there is time for a second look, the door is slammed shut and Zakes is left bewildered and wondering if what he saw was real. Later at a service station, Zakes' fears grow when Beth goes missing, and as he begins a frantic search, he is enticed into a deadly game of cat and mouse on the deserted motorway.