Misaki Suzuhara is a sixth grader who has just moved to Tokyo to live with her aunt. She stumbles across a merchandising phenomenon known as Angelic Layer in which a person can purchase a doll and custom design it. Once their doll is finished, they can link to it through new technology and have it move however they want, as long as its within the confines of a field known as a "layer." In these fields there are battles to see who is the best at Angelic Layer that occur at tourist traps or at special tournaments; Misaki meets a strange man known only as Icchan who gets her involved in the games. The man for some reason believes that she has high potential to become one of the greatest players of all time...
The story is about Rito Yuuki, a high-school boy who cannot confess to the girl of his dreams, Haruna Sairenji. One day when coming home and sulking in the bath-tub, a mysterious nude girl appears out of nowhere. Her name is Lala and she comes from the planet Deviluke, where she is the heir to the throne. Her father wants her to return to her home planet so she can marry one of the husband candidates, but she decides that she wants to marry Rito in order to stay on Earth.
Seventeen-year-old Nanaka Kirisato is a high school student serious about her studies and goals in life. She frequently criticizes her best friend, Nenji Nagihara, for being a childish delinquent who spends his time fighting other boys. Then one day, after a heated argument with Nenji, she falls off a flight of stairs and suffers a brain injury, resulting in her mind reverting to that of a six-year-old. With this in mind, Nanaka's father and Nenji must keep her injury a secret as she struggles to live a normal life and grow up all over again.