The story follows Ryo Takatsuki, Hayato Shingu, Takeshi Tomoe and Kei Kuruma, four teens who discover that their bodies have been genetically engineered.

Despite their differences, they team up and search for answers, leading them to confront an organization called the Egrigori, responsible for the nanomachine technology implanted in their bodies.

The story follows a young man named Ryo Takatsuki, who at the beginning of the series believes that he was in an accident causing his right arm to be severed from his body.

However, as the story progresses, it is revealed that he was actually a test subject for experiments involving genetics and an "ARMS" nanomachine implant, along with three other youths: Hayato Shingu, Takeshi Tomoe and Kei Kuruma.

They all meet under strange circumstances and after many battles they set off on a journey to rescue Ryo's girlfriend Katsumi Akagi, who is kidnapped by the Egrigori, an immense organization founded by Keith White and Doctor Samuel Tillinghast, that operates in the shadows and has bases, research facilities, and agents all over the world, and are the creators of the ARMS technology.