The Makai fight a secret war against the demon forces known as Horrors, evil creatures that manifest themselves through darkness to devour Humanity. On the frontlines are the Makai Knights, given the task of watching over a district and eliminating any Horrors that manifest there. GARO follows the tales of the Knights bearing the title of ‘Golden Knight Garo’, and their duty to vanquish the Horrors and protect Humanity from the darkness.

Kouga Saejima, a Makai Knight that holds the title Golden Knight Garo protects humanity against "Horrors", dark demonic creatures that possess bodies to lure and devour humans. One night, he saves a young woman named Kaoru Mitsuki from a Horror, but in the process she gets stained by its demonic blood. As a rule, a person that has been stained by a Horror’s blood should be cut down (killed) by a Makai Knight to avoid an unbearably painful death in 100 days, despite this rule, Kouga spares Kaoru’s life and vows to purify her before time runs out.

The story follows a young genius university professor who is able to learn any language. He is asked to decipher a code used in wireless communication: the Luger Code, developed by werewolves, enemies to mankind. Startled to find that he cannot decipher the code and desperate to study it, the professor embarks on a journey to capture a living werewolf to aid him.