In 1858 Texas, brothers Ace and Dicky Speck drive a group of shackled black slaves on foot. Among them is Django, sold off and separated from his wife Broomhilda von Shaft, a house slave who speaks German and English. They are stopped by Dr. King Schultz, a German dentist-turned-bounty hunter seeking to buy Django for his knowledge of the three outlaw Brittle brothers, overseers at the plantation of Django's previous owner and for whom Schultz has a warrant. When Ace refuses to sell Django to Schultz and threatens him at gunpoint, Schultz kills him and shoots Dicky's horse in order to pin him to the ground; he advises the freed slaves to take the opportunity for revenge, which they do by shooting him. Schultz offers Django his freedom and $75 in exchange for help tracking down the Brittles.
Django and Schultz kill the Brittle brothers at Spencer "Big Daddy" Bennett's Tennessee plantation. In turn, Bennett pursues them with an armed posse. Schultz ambushes the posse with explosives and Django kills Bennett. Feeling responsible for Django, Schultz agrees to help him find and rescue Broomhilda, and Schultz trains Django to become a bounty hunter. They return to Texas where Django collects his first bounty, keeping the handbill as a memento and for good luck. He and Schultz rack up several bounties before spring when they travel to Mississippi and learn that Broomhilda's new owner is a member of the American gentry Calvin J. Candie, the charming but cruel owner of the "Candyland" plantation, where male slaves are forced to wrestle to the death in brutal "Mandingo" fights.
Schultz and Django hatch a plan: deciding that Candie will refuse to sell Broomhilda if they try to buy her upfront, they will instead offer $12,000 (equivalent to $423,000 in 2023) for one of his best fighters as a pretext to acquiring Broomhilda for a nominal sum. Their intent is to leave the plantation with Broomhilda under the pretense of returning with the purchase money for a fighter. They meet Candie at his gentlemen's club and make the offer. Intrigued, Candie invites them to Candyland. En route, the group encounters Candie's slave trackers who have cornered D'Artagnan, an escapee Mandingo fighter. Django is forced to intervene when Schultz attempts to buy D'Artagnan on the spot to save him. Candie has the trackers' guard dogs maul D'Artagnan to death, visibly upsetting Schultz.
Having told Broomhilda of their plan, Schultz offers to buy her as his escort while negotiating the initial Mandingo deal during dinner. Candie's staunchly loyal and suspicious head house slave Stephen realizes that Broomhilda knows Django, deduces their plan, and alerts Candie. Enraged, Candie alters the deal at gunpoint to sell Broomhilda for $12,000 instead of the fighter; Schultz reluctantly agrees. During the sale's finalization, Candie threatens to kill Broomhilda if Schultz does not shake his hand to seal the deal. Having had enough of Candie's arrogance, Schultz impulsively shoots and kills Candie. Butch Pooch, Candie's bodyguard, kills Schultz, and Django kills Pooch, Candie's lawyer Leonide Moguy, and many of Candie's henchmen in a prolonged gunfight, but is forced to surrender when Broomhilda is taken hostage.
The next morning, the chained Django is tortured and about to be castrated by overseer Billy Crash when Stephen arrives, informing him that Candie's sister Lara, who has taken charge of the plantation, has ordered him to be sold to a mining company and worked to death. En route there along with other slaves, Django devises an escape plan and uses his first handbill to prove to his escorts that he is a bounty hunter. He falsely says that the men on the handbill from his first bounty are at Candyland, and promises the escorts a share of the reward money. Once released and handed a gun, Django immediately kills his escorts, retrieves his clothes and weapons, and returns to Candyland with dynamite.
Recovering Broomhilda's freedom papers from Schultz's corpse, Django bids his deceased mentor goodbye and avenges him and D'Artagnan by killing the trackers. He then frees Broomhilda just as Candie's mourners return from his burial. At the mansion, Django kills Lara, Crash, and the remaining henchmen, releases the two remaining house slaves, and kneecaps Stephen before igniting the dynamite he had planted throughout the mansion. Django and Broomhilda watch from a distance as the mansion explodes before riding off together.
