John Wick takes back his stolen Boss 429 Mustang after killing several of Abram Tarasov's men, the brother of the late Viggo, and later makes peace with him upon doing so. He then takes the car to a chop shop run by his friend Aurelio. Sometime later, John is visited by crime boss Santino D'Antonio, who tells him that he was the one who helped John complete his "impossible task" in the past and allowed him to marry Helen. John swore to a "marker", an unbreakable vow symbolized by a blood red medallion. Santino presents the marker to demand services to John, but declines. In retaliation, Santino destroys John's house with a grenade launcher. John survives the attack and meets with Winston at the Continental Hotel. who tells him that should be reject the marker, he would be violating one of the underworld's two rules: no killing on Continental grounds and honoring every marker. John accepts the commitment and meets with Santino. Santino gives him a job to assassinate his sister Gianna in Rome, so he can claim her seat at the High Table, a council of twelve crime bosses. Santino also sends his bodyguard Ares to observe John.
Arriving in Rome, John infiltrates Gianna's coronation, confronting her in her dressing room. Realizing there is no way out for her, she slits her wrists. As she dies, John ends her suffering by shooting her in the head. As John prepares to leave, he is spotted by her bodyguard Cassian, who recognizes him as the one sent to assassinate her. He pursues John to the catacombs, but Ares and Santino's men double cross him as a means to tie loose ends. John kills the henchmen before fighting Cassian, until the two stumble upon the Rome Continental and are forced to stop their fight. While sharing a drink, John explains why he had to kill Gianna, while Cassian promises he will grant John a quick death as a sign of professional respect.
Julius, the owner of the Rome Continental, arranges safe passage for John back to New York while Santino issues a $7 billion bounty on his head to pretend he is avenging his sister. Once back in the city, numerous assassins try and fail to kill John while Winston visits Santino, warning him that he "stabbed the Devil in the back" and is unprepared for John's wrath. Suffering from his injuries, John once again confronts Cassian in the subway. After a brutal fight, John stabs Cassian in the aorta before sparing him. Seeking help from the Bowery King, John recovers from his injuries and is supplied with an M1911 with seven bullets for each million on the contract. The King tells John that Santino is holding a gala at an art museum, and John heads to the museum where he kills many of Santino's henchmen, including Ares. Santino escapes to the Continental, intending to remain there indefinitely. Despite Winston's warnings, John promptly executes Santino in the lounge.
As a result of his killing of Santino, Winston tells John the bounty has doubled and is offered globally, and for defying the Continental rules, Winston is left with no choice but to declare John "excommunicado", therefore terminating his access and privileges to the underworld. However, Winston gives John a head start providing him with a marker for future use. As he leaves with his dog, John vows to Winston that he will kill any assassin that tries to hunt him and Winston makes a call to enact John's "excommunicado" within an hour.
