Years after the Civil War, bounty hunter Major Marquis Warren is transporting three dead bounties to the town of Red Rock, Wyoming. He hitches a ride on a stagecoach driven by O.B. Jackson. Aboard is John Ruth, a bounty hunter known for bringing in outlaws alive to see them hang; handcuffed to him is fugitive Daisy Domergue, whom Ruth is escorting to Red Rock. Ruth is suspicious of anyone who might steal his claim to the bounty. Ruth and Warren bond over Warren's personal letter from Abraham Lincoln.
Former Lost-Causer militiaman Chris Mannix, who claims he is traveling to Red Rock as the town's new sheriff, persuades Ruth and Warren to let him on the stagecoach. Warren and Ruth form an alliance to protect each other's bounties. Mannix and Warren almost come to blows over their controversial war records.
The group seeks refuge from a blizzard at Minnie's Haberdashery, a stagecoach lodge. They are greeted by Bob, a Mexican, who says the owner, Minnie, is visiting her mother. The other lodgers are Oswaldo Mobray, a hangman; Joe Gage, a quiet cowboy traveling to visit his mother; and Sanford Smithers, a former Confederate general traveling to put his missing son to rest. Suspicious, Ruth disarms all but Warren. As the group eats, Mannix surmises that Warren's Lincoln letter is a forgery. Warren admits this, saying the letter buys him leeway with whites, outraging Ruth. Warren leaves a gun next to Smithers and provokes him into reaching for it by telling Smithers he tortured, raped, and killed Smithers' son. When Smithers pulls a gun, Warren shoots him as revenge for Smithers' execution of black soldiers at the Battle of Baton Rouge.
While everyone is distracted by the confrontation, someone seen only by Daisy poisons the brewing coffee. Ruth and O.B. drink it, causing them to vomit blood, killing O.B. The dying Ruth attacks Daisy, but she kills him with his own gun. Warren disarms Daisy, holds the men at gunpoint and leaves her cuffed to Ruth's corpse. Warren is joined by Mannix, whom Warren trusts because he nearly drank the poisoned coffee. Warren executes Bob, deducing that he is an impostor who killed the lodge owners, as Minnie hates Mexicans and would never leave one to care for the lodge. When Warren threatens to execute Daisy, Gage admits that he poisoned the coffee. A man hiding in the cellar shoots Warren in the genitals. Mobray draws a concealed gun and shoots Mannix, who returns fire, wounding Mobray and forcing Gage against the wall.
Hours earlier, Bob, Mobray, Gage, and a fourth man, Jody, arrive at Minnie's Haberdashery. They murder Minnie and five other bystanders, leaving only Smithers. Jody, Daisy's brother, tells Smithers they plan to ambush Ruth to rescue Daisy; his gang will spare Smithers if he keeps quiet, as they deduce that an extra lodger makes the setup more believable. The bandits dispose of the bodies, hide the evidence, and conceal guns around the lodge. As Ruth's stagecoach arrives, Jody hides in the cellar.
In the present, Mannix and Warren, both seriously wounded, hold Daisy, Gage, and the dying Mobray at gunpoint. They force Jody out of the cellar by threatening to kill Daisy. Jody surrenders and Warren executes him. Daisy claims fifteen of her brother's men are waiting in Red Rock to kill Mannix and ransack the town; if Mannix kills Warren and allows her to escape, the gang will spare him and let him claim the bounties of the deceased except her brother.
As Daisy and Mobray taunt Warren, Warren shoots Daisy in the foot and Mobray in the leg; Mobray soon dies from his wounds. Gage draws a hidden revolver but is shot dead by Mannix and Warren. Warren tries to shoot Daisy but is out of bullets. Mannix calls Daisy's bluff and rejects her offer, but faints from blood loss. Daisy hacks off Ruth's handcuffed arm and frees herself. As she reaches for a gun, Mannix regains consciousness, shoots, and wounds her. Warren persuades Mannix to hang her from the rafters in honor of Ruth. Afterward, as the two men lie dying, Mannix reads aloud Warren's forged Lincoln letter.