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.

Tomoya Okazaki is a third year high school student resentful of his life. His mother passed away from a car accident when he was younger, causing his father to resort to alcohol and cigarettes. This results in fights between the two until Tomoya's shoulder is injured in a fight. Since then, Tomoya has had distant relationships with his father, causing him to become a delinquent over time. While on a walk to school, he meets a strange girl named Nagisa Furukawa who is a year older, but is repeating due to illness. Due to this, she is often alone as most of her friends have moved on. The two begin hanging out and slowly, as time goes by, Tomoya finds his life shifting in a new direction.

Professor Utonium and his son Ken are studying the strange Chemical X. When a mochi cake falls into the formula, it changes into Chemical Z. Ken fires a ray of Chemical Z at a glacier in Tokyo Bay, however that causes strange lights to scatter, some of them aim at three normal girls, Momoko, Miyako, and Kaoru. This gives them the power to transform into superheroes, the Powerpuff Girls Z!

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.

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