In the bustling streets of New York City, John Wick (Keanu Reeves), seeking retribution against the High Table, goes underground under the protection of the Bowery King (Laurence Fishburne). His journey leads him to Morocco, where he confronts the Elder (George Georgiou) and ends his life, but not without a chilling warning: killing him wouldn't alter John's fate, and he would never find peace in death.
Meanwhile, Marquis Vincent Bisset De Gramont (Bill Skarsgård), a member of the High Table, gathers Winston (Ian McShane) and his loyal concierge Charon (Lance Reddick) to disclose that he has been granted infinite resources to hunt down John, blaming Winston for his previous failures. In a cruel act of punishment, he strips Winston of his position, brands him "Ex-Communicado," obliterates the New York Continental after offering an hour for guests to escape, and brutally executes Charon. Winston, feeling the weight of his friend's unjust demise, vows to carry this burden as long as he lives.
The Marquis recruits Caine (Donnie Yen), a blind ex-assassin of the High Table, to eliminate John, using Caine's daughter as leverage to ensure compliance. In his desperate attempt to evade the ever-looming danger, John seeks refuge at the Osaka Continental, overseen by his loyal ally Shimazu Koji (Hiroyuki Sanada). Despite the warnings from Koji's daughter Akira (Rina Sawayama), urging her father not to shelter John, Koji chooses loyalty and friendship. He warns John that the killing of the Elder has dire consequences, and the Osaka Continental could very well be next in line for destruction.
Unease mounts as the Marquis sends Chidi (Marko Zaror) to the Osaka Continental, leading to an explosive confrontation when the High Table's forces escalate their attack. Akira, working alongside John as the hotel's concierge, struggles to evacuate guests just as the High Table decrees the hotel "Deconsecrated." Amidst the chaos, John bravely battles through countless assassins and engages in a fierce showdown with Caine. Unexpectedly, Mr. Nobody (Shamier Anderson), a bounty hunter with ambitions of his own, intervenes, granting John a chance to flee after deciding the current bounty of $20 million isn’t enough to warrant the kill.
After enduring emotional and physical struggles, the wave of violence takes a turn as Akira becomes a casualty, receiving serious injuries from the mercenaries. A wounded Koji fiercely defends John against Caine until Caine is forced to kill him but spares Akira's life. A heartbroken Akira vows vengeance against Caine and desires John to avenge Koji’s death.
The situation escalates when Harbinger, the emissary for the High Table, confronts the Marquis, stating the bloodshed was unwarranted. Despite this, the Marquis remains resolute in extinguishing John's legacy. The stakes rise higher as the Marquis coerces Mr. Nobody into tracking John for a diminished bounty of $23 million. In a desperate bid, John returns to New York, meeting with a wrathful Winston at Charon’s grave. They plot to challenge the Marquis to a duel, a traditional means for John to break free from the High Table's grasp. However, this requires John’s readmission to his former crime family, the Ruska Roma.
Upon arriving in Berlin, John encounters his adoptive sister Katia (Natalia Tena), who lays down a deadly condition for his return: John must eliminate Killa Harkan (Scott Adkins), a High Table member responsible for her father’s death. The stakes heighten as Mr. Nobody informs the Marquis of John's whereabouts, only for the Marquis to assign Mr. Nobody the mission to finish John off.
Katia ultimately unwittingly leads John to Killa. Both Caine and Mr. Nobody, laden with their own motives, are present as they engage in a high-stakes poker game, with life or death hanging in the balance. Utilizing teamwork, John prevails, gaining his rightful status back. Caine intervenes at the last moment, protecting John's life from Mr. Nobody’s intent.
With Winston acting as John's second, they formally present the challenge to the Marquis. In a tense negotiation, the duel’s parameters are set for dawn at Sacré-Coeur; Caine is reluctantly nominated as the Marquis's champion while the stakes continue to escalate. The Marquis, underestimating John's resolve, believes he is merely a ghost in search of a grave.
As the dawn approaches, the Bowery King presents John with a pistol and a state-of-the-art ballistic suit, while the Marquis complicates matters by releasing a new bounty of $26 million on John's head. As John's peril deepens, he confronts an avalanche of assassins intent on thwarting his arrival at the duel. With mere minutes left to spare, Caine unexpectedly joins forces with John to fend off their common enemies, demonstrating that even amidst turmoil, alliances can form.
In a staggering climax, John and Caine engage in the duel where each shot taken reverberates with the weight of their pasts, resulting in a mutual wounding in the second round. Just as the Marquis relinquishes his control over Caine and his daughter, believing his victory assured, John defies expectations, unleashing a fateful final shot—resulting in the Marquis's death.
With the Harbinger granting their newfound freedom, John and Caine are liberated from the High Table's chains, leading to Winston's official restoration as the manager of the New York Continental. Alas, John, reflecting on his tumultuous journey and the love he lost, succumbs to his injuries in a poignant farewell.
In the epilogue, Winston and the Bowery King gather at John's grave, positioned beside his beloved wife, Helen. However, in a gripping post-credits scene, Caine returns to Paris, only to encounter the fierce and revenge-driven Akira.
