One hundred mamodo (known as "mamono/demons" in the original version) go to Earth every 1,000 years to battle to be the king of the mamodo world (referred to as makai in the original, which can be translated as hell). Each mamodo needs a human partner in order to use his or her spell book, and if his or her spell book is burned, the mamodo has to return to the mamodo world. The spell books contain spells that only the human partner can read and must use them for battling other mamodo. The books depend on the human heart to give the spells power. The human and their mamodo gain these spells through experience. They come in different colors for each mamodo. The last mamodo standing without their book burnt is the new mamodo king.

The main human character, Kiyo Takamine (Kiyomaro Takamine in the original version), is a 14-year old boy in junior high school. His father, Seitaro Takamine, discovers an unconscious mamodo named Zatch Bell (Gash Bell in the original version) while in a forest in England. His father sends the mamodo to be Kiyo's mentor. Unlike the other mamodo, Zatch lost his memory of the mamodo world. Kiyo and Zatch are now caught up in the battle to be the king of the mamodos.