After locking herself inside her closet for two years, Shijima Tsukishima finally comes out of isolation to attend high school. However, when she looks at herself in the mirror, she discovers two shimeji mushrooms growing on the top of her head. This odd occurrence, combined with a lack of social ability and being bullied in middle school, leads Shijima to keep to herself when she arrives at school.

While reading alone, Shijima is approached by her classmate, Majime Yamashita, an eccentric girl with a fried egg on her head. Majime pesters Shijima to be her friend, giving her the nickname "Shimeji" upon seeing the mushrooms growing on her head. After enough insistence on friendship, Shimeji gives in and decides to keep Majime company. Shimeji tries to get through a less-than-normal high school life as she explores the mysteries and wonders of this strange world with her new tenacious companion.