Yuki Cross's earliest memory is of a snowy night in winter, when she was attacked by one vampire and was saved by another, Kaname Kuran.Yuki is the adopted daughter of the Headmaster of Cross Academy, Kaien Cross, and has grown up and become a prefect for the school with one main purpose: for vampires to coexist peacefully with humans . Her fellow guardian, Zero Kiryu, a childhood companion whose parents were killed by a pure-blood 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 pure-blood vampire, Shizuka Hio, four years before. Now Yuki must help him fight his curse, as well as recover the lost memories of her past. She must also discover why Kaname, who leads the group of Night class (all of which are also vampires) at Cross Academy as their President, saved her that night and what deep dark secret he is keeping from her.
Sayori "Yori" Wakaba is Yuki's dorm-mate and best friend since junior high. Yori is a very perceptive girl who finds the aura of the Night Class to be scary. She is one of the few girls with no interest in the Night Class and not intimidated by Zero, frequently joining Yuki to tease him while maintaining that Yuki is the only one capable of dealing with him. Then Yori discovers that Yuki is a vampire during the attack on the school, but she accepts Yuki as she is and appears to be more worried over that fact that she would lose her best friend. Because of the recent events at Cross Academy, she is taken to a safe place by Aidou on Yuki's orders. When Aido appears before the Day Class after they are saved from enemy vampires, Sayori takes the initiative to thank him for saving them.
Zero Kiryu is one of the male protagonists of Vampire Knight. Yuki's close friend and the only other Cross Academy Guardian, Zero descends from a noted family of vampire hunters and was trained to be a Vampire Hunter by Toga Yagari. Zero carries an anti-vampire gun named "Bloody Rose," given to him by Kaien Cross. His powers include accelerated healing, vampire detection, ability to withstand pureblood compulsion and most recently the ability to manipulate vines within his body that are an extension of the Bloody Rose.
Four years ago, Zero was taken in by Kaien Cross as the sole survivor of a murderous attack on his family by Shizuka Hio. Zero was bitten during the attack and spent the last four years resisting turning into a vampire — the tattooed symbol on his neck helped suppress the vampire transformation. Due to the attack, Zero developed a deep hatred and distrust of vampires. He kept his vampire secret even from Yuki until bloodlust overwhelmed him and he bit her. Filled with self-loathing, Zero attempts to run away but is stopped by Yuki, who pledges to kill Zero should he fall to level E. To further ensure Zero's vampire nature remains controlled, the headmaster provides Yuki with a bracelet that reacts with Zero's tattoo and paralyzes him. Despite these measures, Zero's body rejects the blood tablets used to sate a vampire's thirst and Yuki convinces Zero to continue drinking her blood.
While Zero harbours romantic feelings for Yuki, he supports her feelings for Kaname Kuran, in particular because Zero is gradually becoming a level E vampire. He is protective of Yuki, preventing her from trading her humanity to Shizuka Hio in exchange for preventing his degenerating into a Level E vampire, swearing never to allow Yuki to become a vampire; knowing this, Kaname Kuran allows Zero to live because Zero would do anything to protect Yuki. However, with Shizuka's death, Zero is forced to drink the blood of a pureblood, Kaname, to delay becoming a level E vampire. Following Zero's discovery that Yuki is actually a pureblood vampire, Zero and Yuki severs their friendship, with Yuki revealing that her vampire side "ate" her other side.
Though Zero is able to maintain his sanity after drinking Kaname's blood, the Hunters Association arrange his arrest and lock him up. During this time, Kaname reveals that his purpose in strengthening Zero is in order for him to protect Yuki and defeat Rido Kuran. Soon afterward, Zero is shot by his twin brother and finally completes the Twin Hunter fragment after he is convinced to "eat" the dying Ichiru. With this act, as a twin vampire hunter of an excellent lineage who has become a vampire and carrying the blood of three purebloods (Yuki, Kaname and by proxy Shizuka), Zero becomes one of the most powerful characters appearing in the series.
Interrupting the battle between Yuki and Rido, Zero declares his former friend his enemy, though they are able to work together and defeat Rido. Zero reveals his intention to kill all pureblood vampires including Yuki, but finds that he cannot bring himself to kill her. Because of his own lingering attachment to her and as someone who made him feel safe, he finds such an act cruel and reveals that he would not mind if Yuki killed him at that moment. However, when Kaname enters the scene, Zero does not hesitate to entangle him with the Bloody Rose, reasserting his desire to "exterminate all the purebloods." Zero realizes that Yuki should be with Kaname; he kisses her and Yuki assures him that she no longer has any worries about the future. As they part ways, Zero tells Yuki he will find her and kill her, and Yuki in turn says she will wait until that day. As Yuki leaves the Academy, they see each other as Zero carries Ichiru's dead body.