A mysterious cell wearing a stylish hat appears before the regular cells, who are bored with just the same (cell division) work over and over again, every day. This mysterious cell lures the regular cells into a mischievous scheme against White Blood Cell and Killer T Cell. The regular cells enjoy working out their everyday, pent-up frustration. But, just who exactly is this cell wearing a stylish hat?

Attacker You! is the story of ambitious and energetic 13-year-old junior high schoolgirl You Hazuki (variously known as "Mila," "Jeanne" or "Juana" in Western dubbed versions of the anime), who moves to Tokyo from Osaka to live with her father Toshihiko, a cameraman recently returned from Peru, and attend school. You's mother is not in the picture, having left when You was very young. Also living with You and her father is her younger brother Sunny, who is very attached to his older sister and tends to follow her everywhere she goes, including to school and to her volleyball matches. You is also curious about Kyushi Tajima, the pretty blonde woman whom she sees covering volleyball games on television, and about why her father becomes very angry whenever You mentions her. You is passionate about volleyball and dreams of one day being a part of Japan's national women's volleyball team in the 1988 Seoul Olympics. She joins her school's girls' volleyball team and quickly becomes one of the top players, although her coach (who is also her homeroom teacher) is brutal and literally slaps his players around when they don't live up to his expectations. You begins a tumultuous friendship with former school volleyball champ and former arch-rival Nami Hayase (French name: "Peggy"), which comes to a head when the two girls join opposing professional teams. She also develops a crush on So Takiki, the captain of the Hikawa boys' volleyball team (known as "Shiro," "Serge" or "Sergio" in various Western versions), and puts as much effort into trying to win his heart as she does into her game.

In the year 2015, more than a decade has passed since the catastrophic event known as Second Impact befell mankind. During this time of recovery, a select few learned of beings known as the Angels—colossal malevolent entities with the intention of triggering the Third Impact and wiping out the rest of humanity.

Called into the city of Tokyo-3 by his father Gendou Ikari, teenager Shinji is thrust headlong into humanity's struggle. Separated from Gendou since the death of his mother, Shinji presumes that his father wishes to repair their shattered familial bonds; instead, he discovers that he was brought to pilot a giant machine capable of fighting the Angels, Evangelion Unit-01. Forced to battle against wave after wave of mankind's greatest threat, the young boy finds himself caught in the middle of a plan that could affect the future of humanity forever.

After inheriting the company from their parents, siblings Yuuhi and Yuamu Oudou have started to work at Ultraterrestrial Trouble Solutions, an organization that hunts aliens. Although they have never encountered aliens before, Yuuhi is desperate to meet one as he believes that an alien has stolen his important item called the "Earthdamar." One day, while searching for extraterrestrial creatures, Yuuhi and Yuamu find a strange spot in the forest where many trees have fallen, forming a scenery similar to a crop circle. As they venture further, they discover a mysterious spaceship and enter it out of curiosity. To their surprise, they come across Yudias Velgear, an alien from the Velgear Star Cluster. As it turns out, Yudias is seeking to learn about Rush Duel—a card game popular among elementary school students—as he believes that it will save his home from a long war. With the siblings agreeing to teach Yudias about Rush Duel, they eventually realize that their first contact with an alien may not be a random coincidence.