The story follows Yugi Muto, a boy who completed an ancient Egyptian artifact known as the Millennium Puzzle, which led to him to inherit a spirit. After defeating his rival, Seto Kaiba, in a game of Duel Monsters, Yugi is approached by Maximillion Pegasus, the creator of Duel Monsters, who uses the power of another Millennium Item, the Millennium Eye, to kidnap the soul of Yugi's grandfather. Joined by his friends Joey Wheeler, Tristan Taylor, and Téa Gardner, Yugi enters Pegasus' Duelist Kingdom tournament, battling against many opponents in order to defeat Pegasus and free his grandfather's soul.
After the tournament, Yugi battles Duke Devlin in Duke's new game, Dungeon Dice Monsters.
Yugi learns that the spirit dwelling within him is a nameless Pharaoh from Egyptian times, who doesn't remember his past. Yugi enters Kaiba's Battle City tournament in order to obtain the three Egyptian God cards needed to unveil the Pharaoh's past. Along the way, Yugi encounters even stronger opponents and more Millennium Items, including Marik Ishtar, the wielder of the Millennium Rod.
Yugi and his friends get sucked into a virtual world run by Noah, the legitimate son of Kaiba's adoptive father, Gozaburo. After defeating Noah and the corrupt former KaibaCorp executives known as the Big Five, their minds are returned to the real world, and the finals of the Battle City tournament commence. Yugi defeats Kaiba and Marik to gain all three Egyptian God cards.
The order of Orichalcos drains the power from the Egyptian God cards and begins gathering souls in order to revive the ancient dragon, Leviathan. Yugi, Joey and Kaiba are each given a legendary dragon card to fight the Orichalcos. Pharaoh faces Dartz, the leader of the order of Orichalcos, to release all of the stolen souls, including those of Yugi, Joey, Kaiba and Pegasus.
Yugi and his friends battle in the KaibaCorp Grand Championship. Yugi wins the championship, and they all finally return home. Meanwhile, Ryo Bakura, the owner of the Millennium Ring, is overcome by the dark spirit within the Ring, which possesses his body and begins collecting the Millennium Items. Yugi and his friends go to Egypt, where Yugi presents the Egyptian God cards in front of a stone tablet related to the Millennium Items and finds himself sucked 5,000 years into the past, to the time when the Pharaoh lived. Pharaoh and the dark spirit of Bakura battle and the Pharaoh discovers more about his life in Egypt. Finally, Yugi and Pharaoh together discover the Pharaoh's true name, Atem, and summon the three Egyptian Gods to defeat Bakura's evil, returning them to the present day. With all the Millennium Items gathered, Yugi and Atem duel. Yugi defeats the spirit so that Atem can return to the afterlife.