It is November 13, 1959. Perry Smith, a dwarfish, dreamy, soft-spoken man of Cherokee Indian and Dutch descent has been paroled from prison for the past few months. He's on a Greyhound Bus drifting from an unknown location to Kansas City and strumming his guitar. A little girl is fascinated by his strumming, but after he spots her, she walks away. He is to meet up with an old prison buddy, Willie Jay. But he's also expecting to meet with Dick Hickock, another former prison buddy from the local area that had written him a letter about a "perfect score" they could make in western Kansas and that he will meet him at the bus terminal.
Dick Hickock is a charming young man from a simple farm family that own a small tract of land and live just outside of Olathe, Kansas, a suburb of Kansas City. His father is ill and dying of cancer. He informs his father that is coughing badly outside the outhouse that he will get them a better place. With his rifle in the backseat of his 1949 Chevrolet, he is ready to pick up Perry and begin his journey.
At the Greyhound terminal in Kansas City, Perry phones the prison chaplain, Reverend James Post, inquiring about his friend Willie Jay. Perry is upset that he has not yet been released from prison and the chaplain warns him not to set foot into Kansas, since his parole has a condition that he is not to do so.
Out in western Kansas in the town of Holcomb, near Garden City, we are introduced of a prosperous farmer by the name of Herbert Clutter and his family. He is a healthy, vigorous, kindly, yet straitlaced man of 48 years of age that has never used tobacco, alcohol, or caffeine in his life and having a glass of milk for breakfast. His beautiful and sweet 16 year old daughter gives him a morning kiss informing him of her busy day ahead and he finds his 15 year old son Kenyon down in the basement, who is sneaking a smoke and painting a box for his older sister's wedding. Herbert smells the smoke and pretends he doesn't know Kenyon is doing it, but knows and dismisses it. Herbert's wife Bonnie is an ailing and frail woman suffering psychosomatic illness and bedridden much of the time.
Back at the Kansas City bus terminal, Perry is in the washroom treating his badly scarred knee that he got years ago from a motorcycle accident. Afterwards, he looks in the mirror and imagines himself performing in Las Vegas in a nightclub with empty chairs, but then Dick notices him and gets him out of his trance. They leave the terminal.
Dick and Perry are on Interstate 670 entering Kansas. Perry has now broken parole entering Kansas. Dick informs him of the "perfect score" about a rich farmer in western Kansas named Herbert Clutter that he was tipped off on by a former prison buddy, Floyd Wells. He was told that Clutter had a safe with probably 10,000 dollars in it and that they could rob it and leave no witnesses, killing everybody in sight. We get to know these two people, Perry, a quiet, introspective, dreamy, but unstable young man and Dick, less intellectual, but more masculine and practical. Dick assures Perry that it was okay he didn't meet up with Willie Jay, because he is "a flaming faggot".
Perry and Dick stop at a hardware store in Emporia purchasing duct tape, rubber gloves, and nylon rope for their victims. At the checkout stand, Dick steals a package of razor blades. They regret not having purchased nylon stockings, but Perry said maybe they could go to a Catholic church and get them after seeing nuns. Dick jokes and says, "yeah, we'll just go barge in like it was a five and dime store".
On the trip we simultaneously see the everyday life of the Clutter family and Perry and Dick traveling. Herbert is writing a check to an insurance salesman for 40,000 in case anything happens to him and they have a television repairman come. Perry and Dick stop at a hamburger stand, Perry dreams of his childhood growing up with his Dutch father and Cherokee mother having rodeos all over the southwest, and they arrive in Garden City and stop at a Fina gas station to refuel. Perry is in the washroom gobbling aspirin and wincing from the pain in his leg and Dick steals some snacks at the counter while his car is being fueled. The Clutter family is about to go to bed and soon afterwards, Perry and Dick arrive at the Clutter house in Holcomb. Perry said they should split and not do this, but Dick talks him into it. They are both slightly drunk.
The next morning, a friend of Nancy's and her parents are repeatedly ringing the doorbell at the Clutter home, but nobody answers. They cautiously enter the home. The girls father finds a severed phone cord and the girl is screaming. Afterwards, police cars and ambulances arrive at the Clutter home to take away the bodies. The postmistress, Sadie Truitt, is surprised at what's going on.
Perry is asleep at a hotel in Olathe and Dick is at his parents modest home eating. He asks his father what happened to the basketball game and told it got interrupted because of a murder that happened in Garden City that's on the news. Dick jokes and declares he's never been so hungry in his life.
Agent Alvin Dewey has been in charge of the case and is a local resident. He and another agent, Roy Church, have been dispatched to investigate the scene. They are trying to recover fingerprints and Dewey can't find a clue as to why they have been robbed, because Herbert Clutter never kept large sums of cash on him and did everything by check. They are later at the courthouse in Garden City seeing a slide show of bloody footprints seen of two different kinds of shoes and Dewey informs the men that the press do not get the information. After reviewing the slideshow, Dewey insists he will give only facts, mainly that Herbert Clutter's throat was cut and that the women were not molested. He meets up with a stern, but friendly and easygoing reporter, Bill Jensen, supposedly Truman Capote's alter ego. They converse alone in the courtroom and can't figure out the case, but Dewey informs him the two older daughters will get the insurance, even though it was written the same night of the murder. Agent Church is at the Clutter home with the housekeeper and she discovers that Kenyon's radio is missing.
Back at the Olathe hotel, Perry and Dick are listening to the investigation on Kenyon's radio. Perry is disgusted that Dick's prison buddy Floyd Wells lied to him about the money and feels that the story is not true about no clues as to who did the crime. Dick tells him to quit worrying, even though he's a witness.
Prisoner Floyd Wells hears the report of the Clutter murders on the radio and is surprised at the 1,000 dollar reward for anybody that has any clue of them. But still the agents have no clue of it. Yet somehow they knew that over 40 dollars in cash was stolen.
Meanwhile about two days later, Perry and Dick are shopping in Kansas City. Dick plans to write a lot of hot checks for a fitted suit for Perry, whom he says is about to get married, an expensive ring, camera, and a television set. Afterwards they leave and are on their way to Mexico to never come back, hoping to score there.
The investigation continues with men dragging a river near the Clutter home to search for the murder weapon. No success. Dewey and Agent Clarence Duntz go back to the Clutter home and find a man staying there they believe to be a suspect, but instead he turns out to be an escaped mental patient occupying the place.
Dewey and Bill Jensen meet at Hartman's Cafe, a small restaurant in Holcomb managed by Bess Hartman, a sassy, no-nonsense woman. Dewey receives an immediate phone call there from Harold Nye, another agent assigned to the case, with a phone call from Lansing, Kansas from Logan Sanford, head of Kansas Bureau of Investigation. There is a confession from Floyd Wells, Dick Hickcok's former cellmate about Floyd being a former hired man for Clutter and how he told Dick about Clutter's place and all the money and a safe that he had and that Dick wanted to rob the place. He explains how Dick was obsessed with the Clutter home, but never took him seriously. Sanford insists on a pickup for parole violation for Hickock and that he's also wanted for passing hot checks.
Perry and Dick cross the border from Laredo, Texas into Mexico, believing they are now safe and sound and off to live the good life.
Somewhere in Nevada in an auto junkyard with a decrepit trailer, Agents Dewey and Church meet with Tex Smith, a man nicknamed "The Lone Wolf" a reclusive, eccentric, yet courteous 60-ish man that is the father of Perry. They inquire of Perry's whereabouts and if he's seen him, but he says he has not seen Perry since his stint in prison, but they do the math and realize he hasn't seen Perry in years. Smith does most of the talking about Perry's background that he feels he learned his lesson and always taught his kids to be truthful, enterprising, sober, and independent, but that his wife that was a Cherokee Indian that took to drunkenness, sleeping with young men, and the kids living with that and that he put a stop to it. Also telling them of the story when Perry joined him in Alaska after getting out of the Army to prospect gold and building a lodge. The agents find the interview pointless in getting Perry captured and leave.
Perry and Dick are living in a decrepit motel somewhere in Mexico. Perry believes that if they sell the car and buy some deep sea diving gear, they can get the buried treasures in the Yucatan Peninsula to get the Cortez jackpot. However, Dick being practical and realistic tells Perry to forget about it and that he's selling his car for $120 to pay their hotel bill, bar, food, and get a bus ticket to Barstow, California. Much to Perry's extreme disappointment, Dick tells him to knock it off, stop dreaming, and that it's all made up.
Dewey and Bill Jensen are back at the Clutter home still trying to find out the motive of the murders. Even with a newspaper article written about how such an incident could happen months before, they still can't figure it out. But Dewey insists that once they are found, they'll hang.
Dick is enjoying himself at the hotel with a prostitute, while Perry is packing his belongings. Perry takes a glimpse of the prostitute and she reminds him of his own mother. He has flashbacks of his mother sleeping with a younger man and drunk while he and his siblings look on. His father catches his mother in the act throwing the man out, slapping her bare back with a belt, and pouring her alcohol all over her back. It's made evident Perry had a very traumatic and unhappy childhood, despite his love and devotion for both of his parents and siblings.
Perry and Dick are somewhere in the California desert hitching a ride. Dick comes up with a plan that Perry sit in the backseat and when Dick asks him to pass him a match, Perry take his belt to garrotte the driver and rob him. An elderly man in a jeep stops, but then drives away and changes his mind. Then Rosey Grier, a black football star of the New York Giants and a friend of his offer them a ride in his pink Cadillac, but they refuse. They end up taking a ride with a traveling salesman they form a friendly relationship with. Dick asks Perry to pass him a match, but just as Perry is about to garrotte the salesman, the man stops the car to pick up a soldier hitchhiking for Christmas.
Agent Harold Nye is at the homestead of Walter Hickock, father of Dick, and discovers a 12 gauge shotgun he suspects is the murder weapon. Mr. Hickock tells the man he can't understand how Dick would ever commit such a crime and tells the detective about Dick's history that he's still a good man despite what has happened, but the detective seems disinterested at the testimony and takes the weapon.
Perry and Dick end up at a barn in a farmhouse somewhere in Iowa and discover a Pontiac convertible with the keys in it and steal the car. Afterwards, they decide to pass a lot of hot checks in Kansas City and swap license plates to avoid detection. Agent Duntz is in Kansas City and got a report of them buying two tires with a hot check at an auto parts store from a worried clerk and tells Dewey about it. They intend to meet Perry and Dick at the Hickock farm. Duntz is going to meet them at the Hickock farm. Perry and Dick are just about to cross into Kansas through a toll booth, but detect a police car. Perry turns the steering wheel around and he and Dick and go back before approaching the toll booth.
Back in Garden City, Alvin Dewey is studying a map of Kansas about their possible travel route, then telephoned that Perry and Dick have eluded detection. He can't figure out why they came back to Kansas, otherwise.
Somewhere in the desert southwest, Perry and Dick pick up a boy and his grandfather. Dick is reluctant, but Perry insists on doing it. They go through it and the boy tells them if they pick up a bunch of old soda bottles, they can make some money. They end up picking up numerous bottles. By the time they drop off the boy and his grandfather in Las Vegas, they make over six dollars from it. Perry and Dick are in good spirits and want to gamble the five dollars. Perry picks up his belongings from the local post office he has picked up from Mexico. Before they can go to the casinos, they are arrested by local police.
Perry and Dick are in the Las Vegas jail and informed they have visitors. Church and Nye are interviewing Hickock and Dewey and Duntz and interviewing Smith. They are initially believed to think they are being charged with passing a series of hot checks and driving a stolen vehicle, but subconsciously realize they are being investigated about the Clutter murders. Both of them are in separate interrogation rooms making up a story that Perry was to go to Fort Scott to get money from his sister, but it turned out she moved, then they slept with a couple of prostitutes in Kansas City that they don't remember the names of. After Dick is inquired about the Clutter murder case, he flies off the handle. But they know Dick is lying about going to Fort Scott because Perry's sister never lived there and the post office is closed Saturday. Perry is told directly by Duntz directly he killed the Clutter family that day. Dick feels they are putting him on, but after they show him proof of the footprints, he spills the beans and admits Perry did all the killing. Dick faints afterwards.
The next day, Perry and Dick are taken from the Las Vegas jail to Garden City, Kansas. Perry tells Alvin Dewey the story of what happened that night. Flashback to November 14, they reluctantly entered the house and did not find the safe, took Herbert Clutter and his son Kenyon down to the basement, with Nancy and the mother upstairs tied up. After a lot of frustration and finding only a small sum of cash, Perry's legs are hurting him and he has a flashback of his father pulling a gun on him saying "I'm the last living thing you're ever going to see". He cut Herbert Clutter's throat, then shot him, then Kenyon, Bonnie, and Nancy Clutter. Perry concludes that his murder of the Clutter's was not personal, he just did it and thought Herbert Clutter was a very nice man.
The next day, they arrive in Garden City, Kansas at the courthouse and both are jailed. Sometime later, their court case is presented by the prosecutor as a motive simply for money and that they need the death penalty, because life imprisonment would mean possible parole in 7 years. He also quotes The Ten Commandments "Thou Shalt Not Kill". Per Bill Jensen, the jury declared the death penalty.
Perry and Dick are taken to Lansing, Kansas to the death row section. They spend the next five years there living a mundane life entirely of sitting in their cell with a weekly shower and only reading and writing material to keep themselves occupied outside their own thoughts. Bill Jensen narrates about the mundane life on death row before execution and that neither one of them would have ever done the crime alone, but together, they formed a third personality, which is the one that did it. Perry spends most of his time painting portraits and Dick doing research about his rights to not be executed. Three times their case went to the Supreme Court and were rejected.
After a little over five years of waiting, Perry and Dick are executed by hanging on April 14, 1965 at the gallows nearby. Dick is the first one and makes a final testimony that he has no hard feelings and is being taken to a better place. During Dick's execution, Perry and Reverend James Post, whom he talked to on the phone at the bus terminal, is present. Perry tells the chaplain about the story of he and his father in Alaska prospecting and building a lodge, but it was a complete failure and not a single client ever came and over time when food was running low, Perry's father got cross and blamed him for being greedy when he was eating a biscuit. They got in a fight and he pulled a gun on Perry saying "I'm the last living thing you're ever going to see", from the vision he had before killing the Clutter's. Perry declares he hates his father, but loves him as well.
Dick has now died from hanging and cut down. Bill Jensen declares to a young reporter that the hangings are not solving anything except three families broken up and more speeches from politicians and everyone passing the buck. Perry is brought over in a police car to be hanged. Right after being brought up to the gallows and before hanging, he envisions the leathery and impersonal hangman looking like his father. The trap door opens and Perry is hanged.