Nero, who is a young demon hunter who lives on the isolated island of Fortuna, is also a member of the Order of the Sword: a religious sect of knights who worship the Legendary Dark Knight Sparda as a God. Dante arrives, and murders The Order's leader, the High Priest Sanctus, in front of the entire congregation. At the same time, an army of demons invade the city, putting everyone, including Nero's love interest Kyrie, in danger. Tasked with stopping Dante by Kyrie's brother Credo, the Captain of the Holy Knights, Nero's journey leads him to discover that he is in fact a descendant of Sparda himself, and Dante is not his enemy. Under orders from Sanctus, Agnus, has been siphoning the power of the long lost Devil Arm Yamato, the sword of Dante's brother Vergil, to create a demonic army, and imbue high-ranking members of the Order with demonic power. To Agnus' shock, the shattered Yamato restores itself in Nero's presence, and flies to Nero's aid. With The Order's plans revealed, Agnus flees to inform the newly resurrected Sanctus.
As Nero sets his sights on The Order, he discovers to his dismay that Credo is part of the conspiracy, until he ends up being deceived as well when they witness Kyrie being kidnapped by a newly revived Sanctus. He intends to use a creature known as Savior to defeat the demon army he's created, as a means of strengthening the people's worship of Sparda. With the Sparda Sword already in his possession, and needing the blood of a descendant of Sparda along with the Yamato, Sanctus captures Nero to power The Savior's core. Dante arrives, with Trish, who was revealed to be a spy within The Order, and makes a promise to the dying Credo to save Nero and Kyrie. Splitting up, Trish evacuates Fortuna's human residents, while Dante destroys all the Hell Gates scattered over Fortuna, and defeats Agnus, reclaiming the Yamato sword for the last time. Confronting the Savior in a sky battle above Fortuna, Dante drives the Yamato through The Savior's chest, where Nero recovers it inside, freeing himself and Kyrie, and defeating Sanctus.
Nero is able to make peace with the power it has given him to protect those he cares about. Before Dante leaves, he decides to entrust Nero with the Yamato, and Kyrie and Nero share their first kiss in the ruins of Fortuna. Back at Dante's office, Lady arrives. As previously revealed in the game, it was Lady who sent Dante and Trish to Fortuna in the first place as The Order had begun butting in on some of her jobs, which was why Trish immediately went undercover to expose The Order's true colours.