An unknown virus brings the world to a sudden end, leaving only children behind. Vampires who systematically arose from the depths of the earth to enslave and reduce them to livestock.
Knowing that Yu wants to leave, Mika acquires a map and gun from vampire noble Ferid Bathory’s mansion and they make their escape from their underground hold.
In a trap, Ferid is waiting for them and he slaughters the orphans ending with Mika before Yu manages to shoot Ferid in the head.
In 2012, the world allegedly comes to an end at the hands of a human-made virus, ravaging the global populace and leaving only children untouched. It is at this time that vampires emerge from the recesses of the earth, likely followed by age-old horrors of the dark thought only to be myth. The vampires sweep the earth and claim it in a single violent stroke, subjugating the remnants of humanity and leading them beneath the surface to safety. This "protection" comes at the price of donating blood to their captors.
Yūichirō Hyakuya (nicknamed Yu) is a member of the vampires' "livestock" and is reading a book explaining how the world ended in the underground city of Sanguinem, just beneath Kyoto. He lives there with the orphanage he was inducted into, just before the viral outbreak four years earlier. Among the children is another boy the same age as Yu named Mikaela Hyakuya (nicknamed Mika) and a girl named Akane Hyakuya. These three watch after the rest of the children, who are too young to fend for themselves. The boys are polar opposites in personality; Yu is a brash, impatient loner while Mika is bright, intelligent, smiling brightly, and making all the children feel safe and protected around him.
One day, Yu muses about having to give blood to his captors and brags about how he plans to slay them all someday. He and Mika run into a vampire not wearing a hood: a noble by the name of Ferid Bathory. Mika gleefully calls after Ferid and runs to him without a hint of distrust, with Yu watching as the vampire caresses his cheek. Mika agrees to meet Ferid at his mansion later on, and Yu learns his best friend had been meeting illicitly with the vampires he so loathed and giving his blood. Mika tries to explain that doing this entitled him to certain advantages, but Yu refused to listen and stormed off.
Akane finds Yu by himself and reminds him they are all family and Yu remembers how they all first met when he was introduced by the Hyakuya Orphanage Director  before the adults began dying en masse with a vampire declaring to them that humanity has destroyed itself.
That evening, the orphanage children enjoy curry thanks to Mika's efforts. Mika does not return until later that night, and Yu asks him what he had to do to get that curry. Yu says that he will sell his blood instead next time. Mika rejects his offer, and Yu scolds him for trying to do everything himself. Yu presses the issue, and Mika starts crying. A moment later, he claims he was just kidding and pulls out a gun and map. The two wake up the other children, setting off to escape Sanguinem that very night.
The children make it to the gates of the city, but Ferid was waiting for them. Ferid slaughters the children in front of Yu and Mika for the sadistic pleasure of crushing Mika's spirit. The two fight back, but Mika is mortally wounded. Yu manages to shoot Ferid in the head while he is distracted by slicing Mika's arm off. Yu is surrounded by the lifeless stares of dead children and Mika, who is bleeding out. At Mika's urging, Yu runs out through the gates as the only survivor of the Hyakuya Orphanage.
He finds a man named Guren Ichinose accompanied by two women who ask him if he will help them exterminate the vampire race. He immediately agrees thus Yu's quest for revenge against the vampires begins in earnest.
- Yūichirō Hyakuya and Mikaela Hyakuya are introduced.
- The first thing seen in the manga is the page of a book, according to which:
- Vampires can be killed if you crush their heads or if you remove their armband device, as they can be killed by ultraviolet light.
- The physical strength of a vampire is seven times that of a human.
- Vampires allow the kids to live in exchange of their blood.
- Mikaela lets Ferid Bathory drink his blood and in exchange he buys him anything he wants.
- The kids met each other four years ago in the Hyakuya Orphanage.
- Yūichirō ended up in the orphanage because his father tried to kill him, his mother spread a rumor that he is the son of a demon, then went insane and killed herself. Mikaela ended up there because he was kicked out of a moving car by his abusive parents and was taken in by the orphanage.
- The virus hit the Hyakuya Orphanage, which the director contracted. Blood suddenly began to pour from the director's mouth and nose, leading to her death.
- Vampires infiltrated the city after a lethal virus spread among humans who were older than 13.
- The vampire troops were under the direct command of the third progenitor and queen of the vampires in Japan, Krul Tepes.
- It was announced by the vampires that from that day on, the children would be in their custody as they gathered them to bring them underground.
- Mikaela steals a gun and a map showing the way outside of the underground world from Ferid.
- Ferid murders all the children except Yūichirō, who shot him in the head with a gun.
- Guren aware of a prophecy, is waiting outside for a survivor.
List of characters in order of appearance:
Manga panels provide a visual overview of the events of chapter 1 with depictions of the characters, Seraph of the End world and scenarios.
- Page 1
- Page 12-13
- Page 18-19
- Page 20-23
- Page 27-28
- Page 34
- Page 38
- Page 47
- Page 60
- Page 72-73
- Page 6