Minato Sahashi, a typical ronin student, finds his life suddenly changed after meeting a strange girl named Musubi. Minato discovers learns that she is a 'Sekirei' and that he is her 'Ashikabi' (ie. Master).

When Minato's landlord evicts him from his apartment, he and Musubi must search for a new place to live. Through a twist of fate, the two encounter a young woman named Miya Asami, who runs a boarding house (Izumo Inn) and are allowed to stay.

Minato takes a job at a local construction site where he meets another Ashikabi, Seo Kaoru. With Seo's help, Minato infiltrates a nearby botanical garden, drawn by visions of a young Sekirei girl named Kusano, after Seo and his Sekireis eliminate a MBI roadblock in front of the garden. Musubi soon arrives and with her help, Minato rescues Kusano, who later makes Minato her Ashikabi.

Minato, Musubi and Kusano are startled by strange events at Izumo Inn. Unknown to him, Minato is being secretly watched by a mysterious girl. When Musubi leaves to gather groceries, she is attacked by a satellite weapon controlled by the mysterious girl who then surprises Minato in the washroom.

The mysterious girl turns out to be Matsu, a Sekirei who has been hiding at the Inn. Matsu becomes Minato's third Sekirei. Minato has dreams of another Sekirei, later identified as Tsukiumi, a Sekirei that despises Ashikabi. Minato and Kusano go looking for her and encounter Seo. Hikari and Hibiki soon arrive chased by Tsukiumi.

Tsukiumi attacks Minato to prove that she doesn't need an Ashikabi, but she cannot release her full power. Hibiki and Hikari show her the power of fully winged Sekirei, but Minato shields her from the attack. Finally understanding Minato's feelings, Tsukiumi becomes his newest Sekirei, leading to a comical homecoming.

Karasuba, a dangerous and lethal Sekirei, pays Musubi a visit at Izumo Inn and reaffirms a promise the two made in the past. MBI Director Minaka initiates the second phase of the Sekirei Plan and blockades Tokyo with armed personnel from MBI's Security Services. Miya establishes new sleeping arrangements at the Inn, to the displeasure of Minato's Sekirei. Yukari and Shiina go shopping, but attract the attention of another Ashikabi.

The fight between Tsukiumi and the 'veiled' Sekirei (Uzume) ends abruptly due to the interference of Sekirei #3, Kazehana. Musubi takes Minato to meet Kuno and her Ashikabi, Haruka. Since Kuno is so weak, Haruka has decided to leave the city, but they have met many obstacles. With Musubi's encouragement, Minato agrees to help them. That night, Kazehana and Uzume stumble into Minato's room in a drunken stupor, causing Minato much grief with his Sekirei in the morning.

Haruka tells the others about how he and Kuno first met. Minato and Musubi take them to see Seo, who gives them information about the Disciplinary Squad and other dangerous Ashikabi in the city. After some 'prompting' from Miya, Seo agrees to help them escape the city. Later that evening, a party is held as Izumo Inn. Despite knowing that Tsukiumi's absence greatly weakens their chances of success, she refuses to help Haruka and Kuno escape, believing their actions to be cowardly.

Karasuba and Natsuo discuss the relationship between Musubi and Sekirei #8, Yume. The escape plan commences. Matsu rushes to the scene on her motorcycle and saves Kusano, after she becomes surrounded by MBI Security Service soldiers. The group makes it to the bridge, but are confronted by Benitsubasa and Haihane, members of the Disciplinary Squad with orders to prevent Kuno and Shiina from leaving Tokyo at all costs.

Minato is in despair as Musubi is down for the count, but refuses to give up, much to Benitsubasa's irritation, who proceeds to deal with him. Battles rage elsewhere as Kuno and Shiina (along with their respective Ashikabi) come under assault from various adversaries, and thus decided to have themselves winged, repulsing the attacks. But in a twist of fate, someone from Karasuba's past comes to Minato's aid in assisting Kuno and Shiina.