John Wick is making his way through Manhattan before he is labeled "excommunicado" for the unauthorized killing of High Table crime lord Santino D'Antonio on the grounds of the New York Continental Hotel,[N 1] which is considered neutral ground. He sends his dog to safety with the concierge, Charon, at the very same hotel. At the New York Public Library, John retrieves a marker medallion and a rosary. He is injured in a fight with Ernest, another hitman, and seeks medical treatment from an underworld doctor, but his $14 million bounty activates before the doctor can finish, forcing John to complete the suturing himself. Upon leaving, he is quickly pursued by various gangs of assassins, all of whom he kills.

John meets with the "Director", the head of the Ruska Roma crime syndicate, where he presents the rosary and demands safe passage to Casablanca. As John was once one of them, the Director reluctantly helps. Meanwhile, a High Table Adjudicator meets with New York Continental manager Winston and the Bowery King, notifying them that they both have seven days to resign from their positions for helping John and indirectly going against the rules of the Table.[N 1] The Adjudicator enlists Zero, a Japanese assassin, and orders him to stab the Director through both of her hands as penance for aiding John. In Casablanca, John meets Sofia, a former friend and manager of the Moroccan Continental.

John presents the marker medallion, which binds Sofia to return a favor from the past, and demands to be directed to the "Elder" – the only person above the High Table. Sofia begrudgingly takes John to Berrada, her former boss, who tells John he may find the Elder by wandering through the desert until he can no longer walk. In exchange, Berrada asks for one of Sofia's dogs. When she refuses he shoots the dog, which survives due to its bulletproof vest. Sofia wants to kill Berrada, but only wounds him at John's warning. They fight their way out of the kasbah and drive into the desert, where she leaves John. Seven days later, the Adjudicator and Zero confront the Bowery King, who refuses to abdicate his position. In response, Zero's students slaughter his men while the King is slashed seven times with a wakizashi as penance. Meanwhile, John collapses in the desert and is brought to the Elder, who asks why he is there; John states that he wants to live to keep the memory of the love he once had with his late wife.[N 2] The Elder agrees to forgive John's transgressions if he kills Winston and remains subservient to the High Table for the remainder of his life. To show his fealty, John severs his ring finger and gives his wedding ring to the Elder.