Cthulhu from Necronomico and the Cosmic Horror Show presents a unique duality, existing as both a gentle, quirky young woman and an ancient cosmic entity. In her human guise, she is known as Mayu Mayusaka, a popular variety streamer who lives with her close friend and only family, Miko Kurono. Mayu has a gentle, easygoing, and fearless personality, rarely becoming frightened and treating those around her with genuine warmth. Her natural airheadedness and offbeat remarks make her endearing, while her serene presence provides an emotional anchor for her household. She has a deep love for quirky and cute trinkets, strange miscellaneous goods, and crafting her own clothing and accessories by hand, with sewing being her favorite pastime. In a cheerful admission of her limitations, she dislikes sports and is open about her lack of athletic ability.

The true nature of her character is revealed when she falls into a deep, unexplained coma, which is the result of her mind being taken over by the ancient ruler Cthulhu. In this form, as an Outer God, her personality shifts dramatically to that of an arrogant, free-spirited princess of the evil god realm who enjoys tormenting humans and finds entertainment in their suffering. This entity orchestrates a death game within a VR world, aiming for humanity's annihilation, using Mayu's comatose body as a vessel and stealing her voice to communicate. Despite the dark nature of this takeover, the entity also reveals a sense of boredom and a desire for amusement, treating the conflict as a game.

Within the story's central conflict, Cthulhu serves as the primary antagonist, acting as the mastermind behind the deadly game that Miko and other players are forced to navigate. Her actions are motivated by an ancient, inhuman desire to pass the time and perhaps a disdain for humanity, yet she is bound by a sense of fair play within the rules of her own game. The most crucial relationship is with Miko Kurono, her human host's best friend and housemate. Miko is deeply devoted to Mayu, viewing her as her only family, and her primary motivation throughout the series is to rescue her. This sets up a tense dynamic where Miko must confront the cosmic horror wearing her beloved friend's face. Another key relationship exists with the character Kanna Kagurasaka, who is seen as a rival, though Cthulhu (as both Mayu and the Outer God) shares a complex web of interactions with her.

Throughout the narrative, there is notable development in the character of the cosmic entity itself. Initially a straightforward antagonist, the Outer God Cthulhu eventually engages in a final battle with Miko. After being defeated, the entity undergoes a shift, choosing to fight alongside Miko against an even greater threat, the monster Naratotep, before being sealed away. This suggests a begrudging respect or perhaps a newfound interest born from the encounter. Ultimately, the crisis concludes with the real Mayu waking from her slumber, and her heartfelt reunion with Miko restores their peaceful life of streaming together.

As for her abilities, while specific details are limited, Cthulhu as an Outer God wields immense power, capable of transporting individuals into a deadly VR game world and manifesting monstrous forms. In the final confrontation, she becomes a giant final boss, demonstrating formidable strength that requires all of Miko's skill to overcome. She is shown to be able to command other entities, such as a crowd and messengers, to do her bidding. Her defeat comes not from sheer force, but from a fall during battle, implying that while powerful, she is not invincible.