After befriending his classmate Tsubasa Hanekawa, Koyomi Araragi, a cynical and lonely high school student, begins to develop a more positive outlook on life. One night while walking home, however, he encounters an ethereal woman with severed limbs, barely clinging to life. Although reluctant at first to help her, Koyomi ultimately agrees to trade his life for hers, and lets her feast on his blood.

Upon waking in an abandoned building, he is horrified to find that he was turned into a nigh-immortal being by the vampire he saved, Kiss-Shot Acerola-Orion Heart-Under-Blade. Thankfully for the desperate young man, there is a way for him to regain his mortality. Assisted by Meme Oshino, an expert in oddities, Koyomi must defeat the three vampire hunters who stole his new master's limbs to restore Kiss-shot's powers. Determined to return to his old life, Koyomi will stop at nothing to accomplish his goal. However, his largest challenge may not lie in overcoming his adversaries—but in preserving his own humanity.