The book begins with a brief history of the Osage tribe. Grann describes how the Osage came into large sums of money when they discovered oil beneath their reservation land. After being forcibly relocated by the United States Government, the Osage settle in Pawhuska, Oklahoma. A shockingly large amount of oil is found in Pawhuska and a number of companies bid on the right to excavate the Osage's oil. A winning bidder is chosen and then a trust is established to give out monthly payments for the oil.
This sets the stage for the many dangers facing the tribe in the period of the 1920s when the events of the book take place. Moving into hsi main narrative, Grann starts the story with the disappearance of Anna Brown, the sister of Mollie Burkhart. Anna is gone for several days, causing her sister a great deal of worry. Anna's body is later found dead by the side of a river, shot twice in the head. Mollie and her family are devastated. The community is subsequently rocked by a second murder. Mollie speaks with the authorities, but their rudimentary forensics and clumsy investigation methods yield few promising leads.
Mollie begins to feel afraid for her life as other members of the tribe are murdered and Anna's killer goes unfound. She is horrified when the home of her sister, Rita, is blown up, killing her, and her young child. Her husband, Bill, is horribly scarred and dies in the hospital a few days later, suffering in extreme agony. Mollie becomes more withdrawn in this period, retreating from public life in the face of her overwhelming grief. Fear abounds in the community, as tribe members hang lights to ward off evil spirits. Eventually, FBI agents arrive on the scene and begin their own investigation.
FBI agent Tom White comes to Pawhuska to investigate the case. Grann depicts White's early life. He served as a Texas Ranger and joined the FBI in the early days of its formation. Grann also writes about how the FBI formed in the aftermath of the Teapot Dome scandal, a series of bribery incidents that occurred between 1921 and 1923 under President Warren G. Harding. In the midst of widespread corruption, White sought to be on the right side of the law. He brings this rigorous approach to bear on the Osage murders, working hard to solve the case.
White begins to work carefully and recreates the events of the day of Anna's death. He takes note of the fact that Anna was seen in a car that night with Bryan Burkhart, brother of Ernest Burkhart, Mollie's husband. Eyewitness accounts of that night invalidate Bryan's claimed alibi and begin to suggest that he might be guilty. Further investigation begins to implicate wealthy landowner William Hale. White continues his pursuit of the killer, despite facing numerous obstacles, including hostility from Hale and his supporters and a large amount of missing physical evidence.
At the same time, Hale attempts to gain community support by paying off people in the community. Then, in a surprising turn of events, Ernest Burkhart confesses prior knowledge of the conspiracy against the Osage, saying Hale, his uncle, orchestrated the killings himself. He details who carried out each of the murders, but stops short of confessing to poisoning Mollie. During this time, Mollie's health worsens considerably, and she appears to be on the brink of death. White begins to build a case against Hale, but then faces a series of frustrating setbacks, as Ernest recants his testimony. In the meantime, Ernest is charged with murder and sentenced to life in prison for his role in planning the bombing of Rita and Bill Smith's home.
White's pursuit of Hale proves successful, as both he and his various henchmen are also charged with the murders. After the case is resolved, White becomes the warden of a large prison and leaves the Bureau. Grann recounts how he spent the rest of his career as a man held in high esteem by his colleagues. White goes on to survive being shot and taken hostage by some of the prisoners. He is remembered by different people in the prison as a tough but fair individual. Concurrently, Mollie remarries and, due to a shift in her legal status, is finally made a full citizen with independent control of her finances. Grann then notes that this case had wider implications for the systemic violence being propagated against the Osage.
Grann describes the present-day conditions of Pawhuska, noting all of the sites that have disappeared from the town, as it has fallen into economic depression. He writes about how, in the present day, Mollie's family and other modern members of the Osage tribe try to preserve their traditional ceremonies. They also talk about the lingering impact of the case and the difficulty Mollie had talking about the murders. Grann speaks with Mollie's granddaughter, Margie, who shows him around town and discusses these issues with him.
Grann then runs down a list of similar murder cases within the Osage tribe. He details many similar instances in which white people married or took legal guardianship of Osage individuals and then killed them to steal their land rights. He makes the case that cases like Mollie's were incredibly common and indicative of widespread systemic violence against Native Americans. The book ends on a somber note, as Grann speaks with a member of the tribe who says the land is saturated with blood.