Killers of the Flower Moon tells the story of the Osage in three related chronicles. The first part details the events as they were unfolding in the 1920s, locating deaths of more than twenty-four members of the Osage Nation within both contemporary and historical context. The first section centralizes on Osage woman Mollie Burkhart, who loses most of her family during what comes to be called the Reign of Terror. The second section narrows in on the U.S. government’s investigation of the murders, led by Agent Tom White of the emerging Bureau of Investigation. White’s team of agents manages to solve a few of the murders, and the section follows their efforts to establish the facts and bring the perpetrators to justice. In its final section, the book moves into the twenty-first century as the author investigates crimes left unsolved nearly a century earlier, working to bring clarity to Osage families still suffering from their losses. 

Although others are killed, the deaths of Mollie Burkhart’s mother, sisters, and brother-in-law are the focus of the first chronicle. In 1921, Anna Brown, Mollie’s older sister, is shot in a car, after having been taken home from a gathering at Mollie’s house. Soon after, other family members also die in short order: Lizzie, Mollie’s mother, wastes away suddenly, while Rita, another sister, and her husband Bill Smith are killed when their home explodes. Mollie’s third sister, Minnie, also passed away abruptly of an unknown disease before the start of the book. Supported by her husband Ernest, Mollie vows to figure out what’s happening to her family. The state of law enforcement in rural Oklahoma in the 1920s is poor and the task of investigating the deaths falls to amateurs or detectives-for-hire. Corruption in the county and the state’s justice systems impede the investigation.  

Well-liked cattleman William Hale, Ernest’s uncle and an important local businessman, offers support. Hale hires detectives and makes a show of wanting justice. The Osage history, which unfolds across this section, should have made Mollie wary of his offers of friendly support. The nation’s westward expansion systematically stripped the Osage and other indigenous people of their territory and the necessities to sustain their traditional way of life, so the Osage ended up purchasing a small plot of undesirable rocky land in Oklahoma. Their luck seemingly changes when oil is discovered on the land. By leasing their land to oil miners, the Osage become per capita the richest people in the world in the early 1900s. Abundant wealth makes them targets, and as many as twenty-four people die in what they come to call the Reign of Terror. Neither local officials nor private eyes can explain the deaths. Osage advocates travel to Washington, D.C., to petition the federal government on the tribe’s behalf. 

The second chronicle delves into the Bureau of Investigation, J. Edgar Hoover, its director, and Tom White, the agent he tasks with solving the crime. At this point, the Bureau is in shambles, rocked by scandals and a poor reputation, and Hoover hopes that solving the Osage murders will help to repair its standing. Although White, a former Texas Ranger, does not match Hoover’s model for the modern Bureau, his upstanding character and knowledge of the West make him the ideal choice to lead in Oklahoma. From a family of Texas lawmen, White is comfortable with a weapon, although, he prefers not to use his. He assembles a task force that includes undercover agents and proceeds to investigate. White carefully sorts fact from fiction, slowly building a picture of the conspiracy at work in Osage County. At the center of this picture is William Hale and his nephews, Ernest and Bryan, but many other prominent white citizens are also involved, including local doctors and merchants. 

When White finally assembles a case that he believes to be built on facts, he strives to ensure the trial of Hale and his main henchman, Ramsey, will proceed without undue pressure. In addition to the fact that racism might influence the jury, there is also Hale’s extensive influence to consider. The prosecution tries unsuccessfully to move the case to federal court, a failure that threatens to doom the process when the first trial ends in a hung jury. The government decides to proceed again, and, this time, Ernest Burkhart cracks, perhaps moved by the death of his youngest daughter, Anna. Ernest eventually pleads guilty to his role in the crimes and then testifies against Hale and Ramsey, who are both found guilty and sentenced to life in prison.  

Mollie had long stood by her husband, but unable to ignore facts, divorces Ernest and wins the right to be her own guardian. Feeling the case is resolved, White leaves the Bureau and becomes the warden of Leavenworth Penitentiary where, for a time, he oversees the imprisonment of Hale and Ramsey. Wounded in an escape attempt, White moves to a different prison and the section overviews his later years, focusing on his efforts to keep the Osage murders and the team that solved them in the public eye. Hoover, however, is not supportive. 

In the third chronicle, after working with descendants of the victims, David Grann realizes the death toll during the Reign of Terror is surely much higher than the official count. He determines that it begins before the 1920s and that it continues past William Hale’s in 1926, well into the 1930s. Looking through guardianship records and traveling between archives, Grann identifies mortality patterns that far exceed the national average, an indication that the conspiracy extended beyond Hale’s web. New villains, like Burt Lawson who admitted to being hired to blow up the Smith’s house, emerge. Grann believes he can explain what happened to some victims, notably Vaughan, but is unable to reconstruct evidence for all the various people who seek his assistance. The book ends as Grann promises yet another person that he will try to provide solve a mystery that has shaped her life, as she cites from the Book of Genesis that the blood-soaked land cries out.