Yuki's earliest memory is of a snowy night in winter, when she was attacked by one vampire and was saved by another, Kaname Kuran. Ten years later, Yuki Cross, the adopted daughter of the headmaster of Cross Academy, has grown up and become a "prefect" (also known as a guardian) for the school with two purposes: to protect the Day class students (humans) from the Night class students (vampires) 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 parents were killed by a pureblood vampire, 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 a pureblood vampire four years before, Shizuka Hiou. Kaname, Yuki's savior, leads the group of Night class, with the help of Takuma Ichijo (the vice president).
The main differences between the anime and manga are the placing of the story and the finer details. Several events with the anime are rearranged (such as when Yuki is attacked, however she is attacked several times in anime). Also, minor details of how Yuki is attacked are also changed. Some scenes and details, like when Zero fires his gun, the Cross Academy symbol is shot out, or when Yuki follows a child with a red balloon or Aido's "Souveneir Collection", which appear in the anime but are not seen in the original manga.