Yuki's earliest memory is of a snowy night in winter, when she was attacked by a vampire and was saved by another, Kuran Kaname. Ten years later, Yuki Cross, the adopted daughter of the headmaster of Cross Academy, has grown up and become a prefect (or guardian) for the school, with two purposes: To protect the Day class students (humans) from the Night class students(vampires) fangs and to protect the true identity of the Night class students from being discovered by the Day class students. Her fellow guardian, Zero Kiryu, a childhood companion whose family was killed by a pureblood vampire (Kuran Kaname is a pureblood, but not the murderer of Zero's family.) is now determined to kill them all and refuses to trust them. Through a cruel twist of fate, Zero becomes a vampire himself, having been bitten by the pure blood vampire four years before. Kaname, Yuki's savior, leads the group of Night class, with the help of Takuma Ichijou.

Yuki is the adopted daughter of the Head master at Cross Academy and is a member of the Discipinary Committee, also known as a Guardian. She, like Chairman Cross, believes that vampires and humans can live together peacefully. She also faces the challenge of trying to save Zero from becoming a Level E, a mad and bloodthirsty vampire. Yuki has no memory of her life before she was 5, due to the work of her mother, Juri Kuran. Yuki now seems distant to Zero and Kaname when she found out Kaname is her brother and is engaged to him.

Zero's family was killed by the pureblood vampire Shizuka Hiou. He was taken in by the headmaster of Cross Academy, and became a Guardian. Yet he has a great hatred for them even though he is now one himself (Level D), due to Shizuka's attack four years ago. It seems that Zero likes Yuki much more than a sister or a friend that it is possible he is in love with Yuki.

Kaname is a pureblood vampire (Level A)that saved Yuki from a Level E vampire 10 years prior to the events of Vampire Knight, when she was 5, and brought her to the headmaster. Also, he is the president of the Night Class and Moon Dormitory, both respected and feared by the members of the Night Class. He has a deep love for Yuki and hurts him to see that she has been giving blood to Zero.