NOTE: This spoiler was submitted by Jeremy

The film starts with a tribe of Osage natives conducting a ceremony to bury a peace pipe. They lament that the white man has arrived on their land, and their descendants will eventually be removed from their homes. Moments later, a group of men come across an oil deposit. Text and clips show that the Osage became the wealthiest people in the country, and it would not be long before others tried to get in on their profits.

Ernest Burkhart (Leonardo DiCaprio) arrives in the Osage Nation in Oklahoma after World War I. He goes to his uncle, William King Hale (Robert DeNiro), an influential figure in the area who has amassed his own wealth through businesses and his job as a reserve deputy sheriff. Ernest’s brother Byron (Scott Shepherd) also lives around. Hale tells Ernest about the Osage’s wealth and how he must jump on the opportunity to profit from them.

In the area, several Osage members have been murdered with no investigations taken. The perpetrators are men working under Hale trying to seize control of their wealth. One woman, Mollie Kyle (Lily Gladstone), lives with her mother Lizzie Q (Tantoo Cardinal), while her sisters Anna Brown (Cara Jade Myers), Rita (JaNae Collins), and Minnie (Jillian Dion) also live in town. She meets Ernest when he gets a job working as a cab driver, and he begins to drive her around. Ernest genuinely develops feelings for Mollie and eventually marries her. During the wedding, Hale notices Minnie looking sad and speaks to her.

Minnie later dies of a “wasting disease” that is affecting some of the Osage. Lizzie is shown to favor Anna over the rest of her daughters, even though Anna is a dysfunctional alcoholic that carries a gun in her purse. During Minnie’s funeral, Lizzie tells Mollie that she saw an owl fly into her room, which is supposed to be an omen of death. Days later, Anna is found murdered after being shot in the head. The doctors in town (who also work for Hale) dismember Anna’s body to supposedly find the bullet.

Hale employs a number of criminals to carry out the murders, including Blackie Thompson (Tommy Schultz), Henry Grammer (Sturgill Simpson), Kelsie Morrison (Louis Cancelmi), and Acie Kirby (Pete Yorn). Mollie speaks to a private investigator, William J. Burns (Gary Basaraba), but Hale sends Ernest and Byron out to assault him to get him off their backs. Ernest also engages in criminal activity, such as gambling with stolen jewelry taken from Osage victims. Meanwhile, Ernest has three children with Mollie – Cowboy, Elizabeth, and a baby named after Anna.

An Osage council discusses the murders and how to respond to them. Their current situation is compared to the Tulsa race riots in the same state. Mollie starts to suffer from the “wasting disease”, worsened by Ernest since he begins to drug her by putting a toxin in her insulin for her diabetes. Baby Anna also begins to suffer from a cough and is taken to get help, even though Mollie will not see traditional doctors.

One local man, Henry Roan (William Belleau), who was Mollie’s first husband before Ernest, is seen around town drinking and bemoaning his mistakes, resigning himself to an early death. One of Hale’s men takes him nearly out of town before clumsily shooting him in the back of the head when he was supposed to make it look like a suicide. Hale then beats Ernest for the botched killing since it now obviously looks like a murder. Another local, Charlie Whitehorn (Anthony J. Harvey), is found dead in a small pool of oil.

Lizzie falls ill, and Mollie and Rita stay by her side as she slowly dies. In her final moments, Lizzie appears to see elder Osage people guiding her to the afterlife. Later, while Ernest and Mollie sleep, an explosion wakes everyone up. It came from Rita’s home that she shares with her husband Bill Smith (Jason Isbell). Ernest goes to investigate and finds Bill begging to be killed after his injuries, while Rita is dead with the back of her head blown out. Ernest returns to his home to confirm to Mollie that Rita didn’t make it, causing her to wail in agony.

Mollie’s health starts to get worse, with her suffering hallucinations and even seeing the same owl that her mother saw. Despite her health, Mollie takes it upon herself to travel to Washington DC to personally speak to President Calvin Coolidge (Mark Landon Smith) so that a proper investigation may be taken into the murders.

Ernest is later visited by Tom White (Jesse Plemons), an agent with the Bureau of Investigation, to ask him about the murders in town. White speaks to Hale as well, who tries to play innocent and feign knowledge of the killings. Hale starts to try and cover his tracks by having some of his men killed afterwards. His efforts are unsuccessful, as White figures out the truth and arrests Ernest and Hale.

Mollie’s health gets to a point where the agents have to intervene and give her proper medical attention, allowing her to heal and return to normal health. Ernest ends up taking some of the toxin for himself and suffers its effects while he is being interrogated. Hale’s attorney W.S. Hamilton (Brendan Fraser) tries to urge Ernest to say that he was beaten and tortured so that he cannot testify, with the implicit threat of harm against him and his family if he refuses to comply. He even relays these lies back to Mollie.

Baby Anna soon dies from the whooping cough. Ernest learns the news from White, which breaks him and causes him to finally turn against Hale and decide to testify against him. During the trial, Ernest speaks to Prosecutor Leaward (John Lithgow) and states that his uncle coerced him into committing crimes against the Osage, but specifically Mollie and her family, so that they may profit off of her wealth. When Leaward asks Ernest if Hale had ordered him to marry Mollie to get closer to her, Ernest says that he genuinely fell in love with Mollie and married her for that. Mollie later privately speaks to Ernest and asks if he has told the whole truth. When she asks what he was injecting in her, Ernest still lies and says it was just insulin. Mollie finally leaves him.

The film then cuts to a radio show having been depicting the film’s events, with an epilogue of what happened to everyone involved. Hale was convicted and sentenced to life in prison, but he and Byron eventually made parole on the condition that Hale never set foot in Oklahoma again, though some eyewitnesses claim to have seen him visit his family. The show’s producer (Martin Scorsese) comes out to read Mollie’s obituary, as she had divorced Ernest and settled down with a new husband before dying at the age of 50 and being buried next to the rest of her deceased family. The murders were also never mentioned.

The final scene is of an Osage drum ceremony in the present day, with the Osage gathered together, singing and dancing, still thriving.

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In the early 20th century, the indigenous Osage nation were the wealthiest people in America. White men came into their land in Oklahoma to "guard" their wealth, but businessman William King Hale employed a number of criminals to murder the Osage to seize control of their profits. Hale's nephew Ernest Burkhart marries Mollie Kyle in an attempt to profit off of her wealth. Mollie's three sisters - Anna, Minnie, and Rita - are all killed, along with Mollie's first husband Henry, and a number of other wealthy Osage.

Mollie falls ill when Ernest begins putting a toxin in her insulin medication. Despite her health, Mollie travels to Washington DC to speak to President Calvin Coolidge and request that an investigation be made into the murders. The Bureau of Investigation sends Tom White to look into the murders. While Hale tries to cover his tracks, he and Ernest are found out and arrested. Ernest is coerced into not testifying against his uncle until his youngest child dies from a whooping cough, which breaks him and leads him to testify. Mollie leaves him after he continues to lie to her when she knows he was drugging her.

An epilogue told in the form of a radio show states that Hale was sentenced to life in prison but eventually let out on parole for good behavior. Mollie divorced Ernest and married another man before dying at the age of 50. While there was no real justice in the murders, the Osage nation continues to thrive today.