Herbert Clutter inspects his ranch on the morning of November 14, 1959. That same morning, on the other side of Kansas, Perry Smith meets up with Dick Hickock. While the Clutters go about their daily business, running errands and baking cherry pies, Hickock and Smith are tuning their car. After a long drive, they pull up to the Clutter home with a shotgun and knife in hand.

That morning, the bodies are discovered by Susan Kidwell and another of Nancy's friends. Initially, the police are baffled. Bobby Rupp is a suspect until he passes a lie detector test. Alvin Dewey, the KBI agent in charge of the investigation, thinks that the killer must be someone close to the family. Rumor sets the small town of Holcomb on fire. Hartman's Cafe is the center of numerous theories.

Meanwhile, Perry and Dick have returned to Dick's hometown of Olathe. Dick passes some hot checks, and the two flee to Mexico. Perry has always dreamed of finding sunken treasure in Mexico. While the investigation in Kansas begins to methodically follow up dead end leads, Perry and Dick spend some time entertaining a rich German tourist before they run out of money in Mexico City. While packing to return to the states, Perry goes through his personal belongings and remembers his childhood. His mother and father rode the rodeo circuit until they had a falling out. Perry was passed from home to home as a child. Now, two of his three siblings have killed themselves.

The investigation of the Clutter murders seems to be heading nowhere. However, a man in the Kansas state prison at Lansing, Floyd Wells, hears of the murder case. Sure that Dick Hickock is responsible, he begins to think of talking to the authorities. Meanwhile, Dick and Perry are hitchhiking in the American desert. They try to steal a car, but fail. By this time, Floyd has confessed, and Dewey and his team are beginning an elaborate manhunt.

Before they are caught, Dick and Perry steal a car, return to Kansas City, pass more hot checks, and take up residence in Miami. They eventually backtrack to Las Vegas, where a policewoman recognizes their license plate number. Dick confesses after intense questioning, and Perry follows suit. The trial goes smoothly, and the two are condemned to death.

During a five-year appeals process, Dick and Perry languish in Death Row. Perry tries to starve himself while Dick writes letters to various appeals organization. They are kept company by various appalling criminals. When death comes, Dick is awkward and Perry is remorseful.