Sasami Tsukuyomi is a high school shut-in who often stays at home and is doted upon by her older brother, Kamiomi. However, due to unknowingly possessing a god's power, Kamiomi's habit of trying to appease Sasami often puts the world into chaos, while the three Yagami sisters try to put a stop to it.
In her report, Sasami explains how she was trained at the Tsukuyomi Shrine to inherit Amaterasu's power, which had been passed down from her family through incestuous means. She soon began to question her life after discovering the internet, eventually deciding to run away with Kamiomi. As she writes her report, Sasami discovers that a third arm has grown out of her chest, soon discovering it has a personality of its own, which tells him Kamiomi plans to return to the shrine in order to protect her from hunters who want Amaterasu's power. Struggling against the sunlight, Sasami comes across Tsurugi, who brings her to Tsukuyomi Shrine and reveals herself to be Amaterasu herself, who gave her power to Sasami's ancestors long ago.
Sasami believes to have seen her mother, Juju, walking through the streets, despite knowing it shouldn't be possible. The next day, Sasami encounters her again and decides to drag her along to go shopping with her. Despite having fun, Sasami inevitably brings up the matter of how Juju could possibly be here as she had already passed away due to an illness. Juju reveals that she negotiated with the king of the underworld following her death to allow her to stay in the mortal world until her corpse rots as she disappointed to hear about Sasami leaving the shrine. Juju attempts to force Sasami back to the shrine to resume her training, believing Sasami to have wasted her life. Tsurugi and the Yagami sisters arrive to fight against Juju, but struggle against the powers the king of the underworld have granted her. Kagami is stabbed whilst Tsurugi is pushed through a gateway to the underworld. Not wanting Tama to get hurt as well, Sasami agrees to go with Juju back to the shrine.
Tamamo-no-Mae reveals she had possessed Sasami when she was young and was awaken when she felt the desire to change the past, using her power to transform the past. As the golem attempts to kill Juju, Sasami's mind is sent to her own body on the day Juju died, where Tsurugi awaits and Juju returns to life due to a spiritual object she put in Sasami's body, which was what was causing her obesity. Deciding the way to stop Tamamo-no-Mae is to eliminate Sasami's feelings of remorse, Tsurugi takes Sasami and Juju to different points in the past to look for clues. Feeling that it isn't right for the Tsukiyomi clan to hold onto a god's power, Sasami decides that Juju should hold onto Amaterasu's power until she grows up, with Juju feeling proud of her conviction. As Tsurugi feels some regret for leaving her power in humanity's hands, Sasami assures her she's done nothing wrong. After overcoming all of their regrets, Juju is able to fight against Tamamo-no-Mae, using the power she received from Sasami to defeat the golem. Back in the present, Juju emerges from Sasami's body, which resumes its normal shape afterwards. Later, Sasami is approached by her school's student council president, Jou Edogawa, who, unbeknownst to Sasami, is part of Arahabaki.
With Jou feeling betrayed by Sasami going after Kagami, she begins to put her plan into operation. Tama is captured and Sasami is cut off from the island whilst Kagami faces up against Tamama-no-Mae. Taking a severed arm into her body, Jou forces Tama to help her with a ritual to allows her to steal Tamama-no-Mae's power, ripping out her organs and summoning a large multi-headed dragon. Tamama-no-Mae attacks with her golem, Sasami manages to break through the barrier surrounding the island and enter Tama's body whilst Kagami defeats the golem, returning the world to normal. After an acqaintance of Tsurugi's defeat the dragon, Sasami finds Jou and rekindles her friendship with her.
As the second year gets underway, Sasami ends up learning Jou's secret that she sometimes grows a penis on her body. Later, Jou announces a class trip to a shrine, but Sasami ends up catching a fever and is unable to go. Wanting to experience the trip for herself, Sasami uses a spell on Tama to have her assume her form so she can go in her place alongside Kagami and Tsurugi whilst Sasami observes what Tama does. When it comes time for everyone to have a bath, Sasami tries to get Tama to help Jou to avoid the others learning her secret, protecting her from Tsurugi's perverted advances. As Sasami states how she wants to become Jou's friend, she declines, saying she will one day have to kill her.
Sasami writes up a report explaining that the chocolate incident was the result of powerful gods appeasing to the wishes of Kamiomi, who unknowingly possesses the powers of the goddess Amaterasu. Meanwhile, many students are absent from school due to becoming engrossed in a fantasy social game. Intrigued by it, Kamiomi and the Yagami sisters borrow Sasami's spare computers to try it for themselves. Sasami, not wanting them to find something wrong with the game and shut it down, preventing her from playing it anymore, tries to interfere with their gaming to no avail and she inevitably reveals herself as a player while attempting to stop their tomfoolery. When a strange dark dragon suddenly appears, absorbing the spirits of all the players, everyone's minds end up getting sucked inside the game itself.
For some reason, Sasami decides to seclude herself in her room over spring break, using her power to create a barrier that seals off her home from the outside world. Feeling this will have implications on the world if it goes on, Kagami, Tama and Kamiomi attempt to break their way inside the barrier, where they are met by Sasami's resistance. After struggling a bit, they are soon joined by Tsurugi, returned from the underworld, who instructs Tama to eat her way into the barrier and bust into Sasami's bedroom. There, they discover the reason for Sasami's seclusion: she had suddenly gotten fat overnight. To explain what happened, Tsurugi shows Sasami the past through the perspective of Juju, learning of a side of her that she never showed to Sasami. Just then, an assassin from the evil society Arahabaki named Tamamo-no-Mae appears with a stone golem, capturing the young Sasami and speaking of changing the future.
Sasami discovers a DVD containing a project by Kamiomi and the Yagami sisters involving them filming her in secret to record her progress. Putting the somewhat perverted nature of the DVD aside, Sasami can't recall doing any of the actions displayed in the video. As Sasami in the video winds up at a mini live concert, it turns out to be a trap set up by the Tsukuyomi Shrine, in which Sasami's father stabs her third arm and allegedly steals her power of Amaterasu. The video soon reaches its climax involving an all out battle between the shrine, the Yagami sisters and government forces trying to obtain an alien Tama came across. Tsurugi then explains that the DVD was made to explain things to Sasami, who is actually revealed to be the third arm, a sarcoma, who lost her memories and assumed she was Sasami and took her form.
Feeling useless following the previous battle, Tama goes in search for Sasami. Meanwhile, as Sasami refuses to return to being a priestess, Juju drugs her so that she may bear a child, claiming that Kamiomi is dead, when he is really just being held captive elsewhere. Using what little strength she has, Kagami manages to teleport Tsurugi's sword to Kamiomi so he can break free and rescue Sasami. Juju stands in her way, but Tama arrives and manages to use teleportation to break Juju's sword with Tsurugi's. Tama then proceeds to eat parts of Juju before she is dragged back into the underworld by Tsurugi. Later, Tsurugi calls Sasami, telling her to look after the other sisters whilst she deals with matters in the underworld.
Feeling a bit isolated in school, Sasami gets Kagami to be friends with her in order to attract more friends. However, Kagami doesn't seem particularly interested since most of Sasami's suggested activities are unneccessary for her as a robot. Later that night, Sasami finds Kagami in a bloodied state, though she still refuses to be open with her. She becomes upset when she sees Kagami allegedly making some other friends, but cheers up after spending some time playing with Tama, who assures her that Kagami appreciates her friendship. Sasami soon comes to realise that the Myriad Gods are attacking Kagami out of jealousy for being chosen by Sasami to be her friend. After catching up to Kagami after she destroying all the gods inhabiting the school, she learns the girls she saw Kagami hang out were possessed by gods which she purified.
Deciding she need a bath herself, Sasami takes direct control to have a bath with Jou, oblivious to her supposed declarations of rivalry due to planning out a ritual. As Sasami decides to invite Jou to a festival later in the evening, Kagami becomes jealous and runs off. Catching up with her, Sasami assures Kagami that she is her most important friend.
Sasami is a hikikomori, who stays at home all day watching her onii-chan interact with others through her computer. On Valentine’s Day, after Sasami gives Kamiomi some chocolate, he unwittingly gives it to Yagami Tama, not knowing the meaning behind Valentine’s. After Tsurugi informs him about the tradition, Kamiomi finds himself wishing for chocolate from Sasami, and inadvertently turns the entire world into chocolate using his power as a god. The Yagami sisters, noticing the abnormality decide to battle the chocolate and return order to the world!