"Highschool of the Dead" is a manga series set in a world suddenly overrun by a mysterious pandemic that turns people into aggressive, flesh-eating zombies. The narrative centers on a group of high school students and their teacher as they navigate the chaos and fight for survival. The story begins at Fujimi High School, where the outbreak occurs during a regular school day. Takashi Komuro, the protagonist, is forced to kill his best friend, Rei Miyamoto's boyfriend, after he becomes infected. This act creates tension between Takashi and Rei, though they eventually reconcile as the group bands together.

The core group includes Takashi, Rei, Saeko Busujima, a skilled kendo practitioner, Kouta Hirano, a gun enthusiast, Saya Takagi, a sharp and resourceful classmate, and Shizuka Marikawa, their school nurse. Each character brings unique skills and personalities to the group, contributing to their survival. As they flee the school, they encounter various threats, including both zombies and hostile humans, while searching for safety and answers about the outbreak.

The group faces numerous challenges, including rescuing Saya's younger sister, Alice Maresato, from a zombie-infested shopping mall, and dealing with the moral dilemmas of killing infected loved ones. They also confront human adversaries, such as a group of armed survivors who exploit the chaos for their own gain. The series explores themes of trust, leadership, and the fragility of societal norms in the face of disaster.

Throughout the story, the characters grapple with their own fears and insecurities while forming bonds that help them endure. The narrative is punctuated by intense action sequences, strategic planning, and moments of emotional vulnerability. The manga blends survival horror with elements of drama and character development, creating a tense and engaging storyline. The series concludes with the group continuing their journey, leaving their ultimate fate unresolved as they face an uncertain future in a world overrun by the undead.