OH LUCY! follows Setsuko, a single, emotionally unfulfilled woman, seemingly stuck with a drab, meaningless life in Tokyo. Until she's convinced by her niece to enroll in an English class that requires her to wear a blonde wig and take on an American alter ego named "Lucy." Setsuko quickly develops romantic feelings for her American instructor, John. When John suddenly disappears from class, Setsuko travels halfway around the world in search of him.