High school sophomore Miki Koishikawa returns home expecting a normal evening, only to have her cheerful parents announce they are divorcing. They reveal they met another couple, the Matsuuras, while on vacation in Hawaii and have decided to swap partners, with Miki's father marrying Mrs. Matsuura and her mother marrying Mr. Matsuura. To make the arrangement even more unconventional, both families plan to live together in one house. At a tense dinner to meet the other family, Miki is introduced to their handsome and seemingly aloof son, Yuu Matsuura, who is her age. Despite her initial shock and resistance, Miki reluctantly agrees to the bizarre living situation.

The story is set in contemporary Japan, where Miki and Yuu navigate high school life under the same roof as new step-siblings. As they adjust to their blended family, Miki finds herself conflicted by her growing attraction to Yuu, whom she nicknames Marmalade Boy for his sweet exterior masking a bitter inside. Yuu, who is more reserved and athletic, also begins to develop feelings for her. Their budding romance is immediately complicated by the presence of other suitors. Miki is pursued by Ginta Suou, a childhood friend and her former crush, while Yuu deals with Arimi Suzuki, a beautiful and persistent ex-girlfriend from his past.

Several notable narrative arcs test the strength of Miki and Yuu's relationship. A significant subplot involves Miki's best friend, Meiko Akizuki, who is engaged in a secret and socially forbidden romance with a teacher, Shinichi Namura. The central couple also faces challenges from jealous rivals who attempt to sabotage their relationship. The most dramatic arc occurs when Yuu discovers information that leads him to believe he and Miki might be blood-related half-siblings. This revelation causes him to break up with her to protect her from the social stigma, leading to a period of intense heartbreak before the truth about his paternity is resolved. Through these trials involving family secrets, past relationships, and personal insecurities, Miki and Yuu must decide if their love can survive the extraordinary circumstances that brought them together.