Tomboy Ryouko Ookami is a fierce boxer and the assigned bruiser of her club. Of course, no normal high school club needs a bruiser, but the Otogi Bank operates more akin to an actual bank. Here, the students can ask for favors from the club as long as they promise to return the favor in the future. Sixteen-year-old Ryoushi Morino is a shy boy, a far cry from the Otogi Bank members. To his biggest surprise, after unsuccessfully confessing to Ryouko, he inadvertently finds himself joining the club! Ookami-san to Shichinin no Nakama-tachi follows the everyday lives of the Otogi Bank members as they tackle favors that range from the mundane to the dangerous. However, since Ryoushi's sole motivation is to win Ryouko over, she doubts he will be able to have her back in a fight, especially when he can't even stand having people look at him—much less fight anyone!

On November 23, 1957, the whole world witnessed the Federal Republic of Zirnitra's monumental achievement of sending the first live animal—a dog—to outer space. Since then, the space race between the confederacy and its competitor, the United Kingdom of Arnack, has intensified; the two countries hope to one day send humans to the cosmos above. As a dog's biology is inherently different from a human's anatomy, there is no way to perfectly identify the risks involving space travel and its effects on an individual's body without actually sending someone for observation. However, Zirnitra's government has a potential solution: to experiment on vampires, whose biological similarity to humans is too significant to ignore. Despite being forcibly taken from her home in the mountains, vampire Irina Luminesk shows no resistance and is even willing to train as a test subject. Lev Leps, a former top candidate to become the first human cosmonaut, is designated to accompany Irina and act as her guide. Through their time together, Irina and Lev begin to develop a mutual love for outer space, bringing them closer together.

Within everyone there exists a side preferably kept hidden, even from close friends. For the smart and popular Kyouko Hori, it's the fact that she has to do all the housework and care for her little brother, Souta, because of her parents' busy work schedules. For the gentle Izumi Miyamura, whom everybody sees as an otaku, it's his nine hidden piercings and large body tattoo. So what happens when they accidentally discover each other's hidden sides? Sharing parts of themselves that they couldn't with anyone else, strong bonds of friendship soon begin to form between Miyamura and Hori, as well as those around them. As their hidden personas start to dissipate, they slowly learn how to open up to others.

Kaoruko Chaos Moeta is a young manga artist who is down on her luck. She wants to draw manga about high school girls, but her storyboards are bland, her art uninspired, and her premises weak. Her concerned, exasperated editor comes up with an idea: push Chaos to be more social. So, by her recommendation, Chaos moves into a dormitory for female manga artists. She soon meets the other residents: Tsubasa Katsuki, a shounen manga artist; Ruki Irokawa, who draws erotic manga popular with women; and Koyume Koizuka, a shoujo artist who, like Chaos, has yet to be serialized. Quickly striking up a friendship with these girls, Chaos finds new inspiration for her manga and continues to grow her creativity. Comic Girls is a showcase of the daily lives of these manga artists. Will Chaos finally be able to make her debut and become serialized? None of the girls know, but they will all do their best to help each other become the best artists they can be.