- When Jeanne's soul is dragged into the depths of Inferno after a demon summoning goes horribly wrong, Bayonetta goes on a dangerous quest to Inferno to rescue her friend before its too late.
- In the middle of a bustling city during the holiday season a few months after the events of the first game, Bayonetta is doing some Christmas shopping with Enzo in tow to carry her large amount of presents, meeting Jeanne in the process. The trip is interrupted when angels hijack a performance of the Platinum Stars stunt plane team, forcing Bayonetta to suit up and fight back. Eventually, after receiving a new set of guns from Rodin and teaming up with Jeanne to take down Belief, things take a turn for the worse when the demonic dragon Gomorrah escapes his portal after being summoned, attacking Jeanne and causing her soul to be dragged down to Inferno as part of a witch's pact. Despite being able to put down Gomorrah, Bayonetta is left with her friend's lifeless body.
At the Gates Of Hell, Bayonetta says that she intends to rescue her friend from Inferno, an act which Rodin claims does not have odds in her favor. Nonetheless, he also explains how she only has a limited amount of time to save Jeanne before she becomes permanently trapped in Inferno for good and says that he will put Jeanne's body 'on ice' to preserve it. She is told that reuniting Jeanne's soul with her Umbran Watch, the source of an Umbra Witch's eternal life, is the only way to get her out. With this in mind, Bayonetta snags Enzo and makes him take her to the sacred mountain Fimbulventr. It is said that the mountain is the only place on Earth that connects the human realm to both Inferno and Paradiso. Enzo also mentions information that the portal to Inferno, the literal Gates of Hell, is hidden there and it has so far never been discovered by human hands.
Bayonetta arrives in the city at the base of the mountain, Noatun, to find a way to get into Inferno and rescue Jeanne from her fate. She meets a mysterious boy in Purgatorio named Loki, who expresses his surprise that she can see and interact with him. The boy is hounded by the angels who seem to want to take prevent him from reaching the mountain. Sensing that their goals to reach the mountain are the same, Loki strikes a deal with Bayonetta to get both of them to Fimbulventr whilst explaining that she will need his powers to get her inside. Luka also arrives in Noatun shortly after Bayonetta's arrival, offering to find out any extra information that can help her find the gateway to Inferno. The journey to the mountain suffers various setbacks from angels and demons alike and Bayonetta also finds herself facing off against a Lumen Sage who seems intent on killing her guide.
Eventually, Bayonetta and Loki reach the Gates, only to be stopped in their tracks by the Masked Lumen and an astral projection of Loptr, a mysterious being who seems to know Loki personally. Unable to prevent the Sage from attacking Loki, Bayonetta manages to hold her own against Loptr until he beats her back. Loptr encourages her to 'see' with the power of the Left Eye and shows her a vision of the past using the Remembrance of Time. Bayonetta is shocked to see that her father was not responsible for the Witch Hunts and that he tried to save her mother from her death before he was snatched away. She also sees a figure that looks like Loki as the murderer. As Loptr explains that it is the truth as it really happened, the Masked Lumen prepares to strike Loki down. The boy fires his cards at the Gates and tells Bayonetta to jump in with him to escape. She complies and wakes to find herself in Inferno. Realising she has little time to rescue Jeanne, she makes her way into its depths.
Bayonetta eventually meets the Demoness Alraune inside her palace, learning that she has taken Jeanne's soul for her own in order to become more powerful. Realising that Bayonetta is an Umbra Witch as well as the fact she has a pact with Madama Butterfly, Alraune savagely attacks but is no match for Bayonetta's powers. Before the witch can deal the final blow, Rodin intervenes and instead seals Alraune in a new weapon. Bayonetta finally rescues Jeanne's soul and reunites it with the watch. When her friend doesn't initially wake up, Bayonetta falters and pleads with her to open her eyes. Jeanne then wakes up to Bayonetta's relief and begins to return to her body. As she leaves, Jeanne warns Bayonetta that something big is going to happen to the world. With her mission complete, Bayonetta turns her attention back to Loki, who she sees being attacked by the Masked Lumen. Interfering in his revenge once again, the Masked Lumen sheds his mask and reveals himself to be a younger Balder. Just as he has gained the upper hand in a fight, Loki suddenly reappears and lets out an uncontrollable shockwave of blue energy, sweeping up Balder and Bayonetta into it.
Bayonetta wakes and realises she is 500 years in the past in Vigrid, during the Witch Hunts. To her shock, she meets Rosa alive and well and the two witches team up to fight back against the influx of angels determined to destroy their sanctuary. Aiding her mother in combat with both her powers and Umbran Armour, Bayonetta meets the younger version of Loptr, Loki's doppelganger. It's here that she realises her mother's eventual murderer would be at the hands of Loptr, not Loki, and she is blasted away in an explosion to the Crescent Valley. Balder, who has been transported back in time with her, enters the sanctuary to find Loptr having just killed Rosa. Bayonetta figures out that that Loptr is the one Balder should be seeking revenge for and not Loki. She opens a portal back to the present and implores her father to follow her, whispering 'Mummy...' under her breath in a final farewell to Rosa. In the present day, Loki has managed to escape Inferno thanks to his powers and is found by Luka. He implores the journalist to take him to the mountain, having remembered who he really is and that he has to stop the evil that is 'all that's left'. Loptr then apprehends both of them.
In the present day, with the help of Jeanne and a fighter jet, Bayonetta and Balder arrive at the top of Fimbulventr and witness the older Loptr having taken hold of Loki. Loptr explains that he and Loki were once two halves of the same soul and that together they were originally the God of Chaos, Aesir. The good part of Aesir, which would eventually become Loki, had decided to split his very soul apart when he had divided his power into the Eyes of the World to maintain the balance that such a division would bring. Loki was given the Sovereign power, the power to control the Eyes as he saw fit where as Loptr, now revealed to be the evil half of Aesir, had been given the Prophetic power and the ability to oversee history using the Remembrance of Time. Feeling that he needed his power back, Loptr had decided to take the Eyes back for his own use 500 years in the past and regain Aesir's power to rule over the realm. However, Loki had escaped to the future by realising Loptr would need his power and had subsequently lost his memory in the process. Loptr would need to wait to find his 'better half' again in order to gain the power to take the Eyes and decided to bring the younger Balder to the present because his older self had died along with the Right Eye after Bayonetta defeated Jubileus. Balder promptly has the Right Eye taken from him. Bayonetta fights back valiantly against Loptr, but is ultimately subdued and has the Left Eye taken as well. Loptr, now having gained the power of his original self and become Aesir, mocks human free will and claims that he is the rightful ruler of the human realm of chaos. Whilst Bayonetta and Balder fight back against the deity, Loki remembers his hidden power besides his ability to control the Eyes. Claiming that the real power of Aesir is over "nothingness" and the ability to erase anything he wants from the world, Loki uses that power to destroy the Eyes from the present and weaken Loptr back to his original state. Bayonetta and Balder then perform a summon together and bring forth a fusion of Jubileus and Queen Sheba. The hybrid kicks Loptr, propelling his physical body out to the ocean where a Jeanne-summoned Gomorrah lies in wait to swallow him whole.
As Loptr's soul tries to escape to the spirit realm to be reborn elsewhere and try his plan again, Balder intervenes and absorbs him despite warnings from Loki that Loptr will corrupt him forever if he remains inside. Balder is content with the sacrifice to show the strength of human free will and reveals that he knew Bayonetta was Cereza all along. He makes her promise to be the one to stop him should he ever stray from his path thanks to Loptr's influence and she obliges in his request to call him "Daddy" once more. She cries after him when he is transported back into his time, finally realising that he was not to blame for his schemes with Jubileus. Loki, having now done what he set out to do and restored the balance to the world with the destruction of both Eyes, begins to fade away. Bayonetta asks whether she'll see him again the boy replies that they may do so in the future when he is reborn again after taking a break. He remarks that she still doesn't strike him as a Cereza before disappearing in a blue haze.
Several days pass since the events at Fimbulventr and both Bayonetta and Jeanne are enjoying another shopping trip to take advantage of the after holiday sales. As the pair witness Luka helping Rodin out with advertising his bar, a woman and a baby in a pram walk by just as one of Loki's cards flutters out of it, implying that his return would be sooner than Bayonetta thought. Bayonetta then remembers that she completely forgot about Enzo back in Noatun. Enzo returns in a crash landing down the street in the plane he was left in with angels in pursuit. Despite her annoyance at ruining a second dress in a month, Bayonetta takes to the plane's wings with Jeanne to fight against their aggressors as they always have.
In a post-credits scene, Balder is shown returning to his time period, now corrupted by the evil of Loptr's soul. Donning his golden mask from the first game, he begins his plot to reunite the three universes, thus setting up the events of the first Bayonetta.
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