The game opens with Nero hurrying towards the central Opera House where the Order of the Sword is conducting a ceremony, his right arm in a sling. Meanwhile Kyrie, Nero’s romantic interest, is beginning to open the ceremony with a song and is disappointed not to find Nero in the audience. She begins her song none the less as Nero encounters several Scarecrow demons on his way to the Opera House; he easily dispatches them without breaking his stride and arrives at the Opera House just in time to hear the end of Kyrie’s song.
Following this, Kyrie joins Nero in the audience where she finds Nero has left a present for her in the form of a gold necklace. The High Priest of the Order of the Sword Sanctus beckons the Order members to join him in prayer; Nero is visibly bored by this and is about to leave despite Kyrie’s protests when his right arm begins to glow ominously. At this moment, Dante bursts through the ceiling and assassinates Sanctus.
The knights quickly rally to avenge their fallen leader but are easily dispatched by the assassin. Nero, under the impression that Kyrie is in danger, attacks Dante initiating a fight between the two. As Dante gains the upper hand, Nero reveals his demonic right arm named the Devil Bringer and uses its power to seemingly kill Dante by impaling him with his own sword, only to find that Dante survived relatively unharmed. Dante comments on Nero’s power before quickly departing after showing Nero that the knights he killed were not human but possessed a demonic appearance.
Nero is charged with capturing Dante and bringing him back to the Order to answer for his crimes by Credo, the leader of the Orders knights and Kyrie’s brother. Upon leaving the Opera House however, a demonic horde begins to lay waste to the city. Nero and Kyrie are separated as Nero begins to slay the demons. Nero fights his way into the depths of Fortuna Castle, on the way, the player is allowed to witness a scene revealing that Sanctus has been infused with the soul of a demon to revive him. The player is also introduced to Agnus, the stuttering scientist and mastermind of the Orders demonic power manipulation.
Nero finally reaches Agnus' facility where he is defeated and heavily injured, the broken Katana Yamato responds to Nero and mends itself before flying into his hand. Nero fends off Agnus' attacks with the aid of a spectral blue demon hovering behind him before he collapses in exhaustion.
Agnus flees back to Sanctus and informs him of Nero’s new-found power, Credo vows to take care of Nero before while Gloria takes over Nero’s pursuit of Dante.
Nero is confronted by Credo who also has been infused with demonic power, giving him the characteristics of an Angel, yet is defeated by Nero. However, Kyrie arrives in time to witness Nero with his demonic arm standing over her defeated brother. Agnus uses the confusion and distraction on Nero’s part to kidnap Kyrie and flee. Credo postpones his feud with Nero until he can investigate the situation. Nero then once more meets Dante, his quest to capture him long since forgotten; he wishes to simply pass Dante by. Dante however, wants Yamato, the sword used by his twin-brother Vergil, returned to him. A fight ensues where Dante is victorious; however, he decides to let Nero keep Yamato after the latter has “cooled down”. Following this is, it is revealed that Gloria is in fact Trish, Dante’s partner in his demon hunting business “Devil May Cry.”
Nero reaches Sanctus and “The Savior” an enormous statue which the Order intends to bring to life using Nero and Yamato’s power. Using Kyrie as a human shield, Sanctus is successful in detaining Nero. Sanctus reveals that the Savior requires the essence of Sparda to be reach full power, he origionally intended Dante be used as the core but accepts Nero as a suitable substitute. Credo attempts to rescue the two but is mortally wounded by Sanctus, Dante arrives and requests Nero give him his sword back. As Nero is absorbed into The Savior, he requests Dante “come and get it.”
Agnus uses Yamato to open an enormous Hellgate releasing a multitude of demons onto the city; Sanctus arrives with The Savior and begins to exterminate the demons. Dante, upon hearing Credo’s dying request to rescue Kyrie and Nero fights his way back towards the city, on his way he destroys the three smaller Hellgates used to release the demons.
Dante arrives back at the Opera House and kills Agnus, he then retrieves Yamato and uses it to destroy the largest of the Hellgates before confronting Sanctus and The Savior. After discovering that The Savior is invincible from the outside, Dante drives Yamato into the chest of The Savior where it is retrieved by Nero. Nero defeats Sanctus inside The Savior and rescues Kyrie; finally, Nero uses the powers of his Devil Bringer to destroy The Savior and Sanctus once and for all. Dante departs after entrusting Nero with Yamato. Nero and Kyrie’s tender reunion is interrupted by another demon attack; Nero draws his sword and begins the fight as the credits roll and the game ends.
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