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.

In the 25th century, a spaceship carrying 300 people leaves the earth in search of a new world in the solar system, but an unexpected accident occurs. They crash into a black hole which is connected to another universe. The people on the ship are cast adrift in an emergency capsule to a planet called Ismo. The story begins 12 years after they have reached Ismo. Ismo is a star of the Onam System, which corresponds to the Solar System in our universe. It is the only planet left in the Onam System. The Death Star called Yomi is a comet which regularly approaches the Onam System.

On the planet Maris in the year 2387 three teen soldiers fight back against invading aliens.