Makai Law decrees that any human stained by the blood of a Horror should be killed, or else they will die painfully in 100 days. This is the fate that has befallen Kaoru, a young girl caught in the middle of a fight between a Horror and a Makai Knight. Kouga Saejima—the Golden Knight Garo—defies this rule, and vows to find a way to purify Kaoru before her time is up.

Now Knight to the Senate, Kouga finds himself marked for death with the Seal of Destruction. Teaming up with old rival Rei Suzumura—Zero—and a young Makai Priest named Leo, Kouga races to find a way to save himself from fate.

In a distant future, the Garo armour has lost its golden shine, and its power as a consequence. The new holder of the Garo title—Ryuga Dogai—is summoned to the metropolis of Volcity and tasked with eliminating the Madou Horrors, a rare breed of Horror, who have infested it. Who are the Madou Horrors, and what is their connection to the lost shine of the Garo armour?

Garo: The Makai Flower follows the adventures of Raiga Saejima, son of Kouga Saejima and Kaoru Mitsuki while he tries to prevent the resurrection the demonic flower of destruction Eris.

After the events of The One to Shine Light into the Darkness, Ryuga Dougai, the current Garo, is assigned to oversee matters in Line City alongside the Makai Priestess Rian. There, meeting new allies and enemies alike, the two first face a rogue Madōgu who sees humanity's destruction as the only way to end the Horror threat and then a pair of Horrors who were once Makai Order members that are intent to revive an ancient Horror.