One fateful day, Yuusuke Urameshi, a 14-year-old delinquent with a dim future, gets a miraculous chance to turn it all around when he throws himself in front of a moving car to save a young boy. His ultimate sacrifice is so out of character that the authorities of the spirit realm are not yet prepared to let him pass on. Koenma, heir to the throne of the spirit realm, offers Yuusuke an opportunity to regain his life through completion of a series of tasks. With the guidance of the death god Botan, he is to thwart evil presences on Earth as a Spirit Detective. To help him on his venture, Yuusuke enlists ex-rival Kazuma Kuwabara, and two demons, Hiei and Kurama, who have criminal pasts. Together, they train and battle against enemies who would threaten humanity's very existence.

In the bustling and futuristic city of Heartland, a young boy named Yuuma Tsukumo has a dream that everyone his age wants to achieve—earning the title of the greatest duelist! Sadly, due to his lackluster dueling skills, this dream is far from achievable. But when the school bully, Ryouga Shark Kamishiro, splits the key given to him by his father into two pieces, he inadvertently sets Yuuma on a collision course with his dream. Retaining one half of the key, Yuuma begins a duel with Shark, but soon realizes that his inexperienced skills are no match for him. In a sudden turn of events, Yuuma's key repairs itself, and the Door of Destiny'' appears before him. Using the key to open it, Yuuma is greeted by an alien by the name of Astral—a being only he can see. The bewildered Yuuma soon learns that his memories have been divided into 100 Number Cards, all of which he must retrieve. However, he is also not the only one looking for them. Bombarded by these revelations, Yuuma, alongside Astral, must defend the world from the upcoming threats that loom over Heartland City—regardless of any divine intervention that may occur.

Yuusei Fudou is out to get back what was stolen from him. The world of dueling has evolved, with Riding Duels becoming the peak of entertainment for the residents of Neo Domino City. They are played on D-Wheels, a hybrid between Duel Disks and motorbikes. After the mechanically skilled Yuusei managed to build his own D-Wheel, his former friend Jack Atlas stole it alongside Yuusei's best card, Stardust Dragon; ditching their decrepit hometown of Satellite, he escaped to Neo Domino City. In the two years since then, Jack has risen to the top of the dueling world, while Yuusei has been making preparations thanks to the help of his friends. With his new D-Wheel finished, he now sets off to Neo Domino City, his only goal to find Jack. Unbeknownst to either of them, there are far bigger things at stake than they can imagine, with puppeteers pulling the strings behind the scenes.

Bullies often target someone frail and weak—someone exactly like Yuugi Mutou. His beautiful childhood friend, Anzu Mazaki, is always there to stand up for him, but he can't depend on her forever. Katsuya Jonouchi, who is almost always accompanied by his verbal sparring partner Hiroto Honda, doesn't seem like a bad person either, despite always bringing Yuugi trouble. But most of all, Yuugi wishes for a true friend who understands him and would never betray him. Yuugi treasures his Millennium Puzzle, an ancient Egyptian artifact that was brought into his grandfather's game shop. Believing that solving the puzzle will grant him his wish, he completes the puzzle, unleashing a new personality within him—the soul of the King of Games. Dark, twisted, strong, and reliable, the new personality named Yami Yuugi is the exact opposite of Yuugi. Upon any injustice toward him, Yami Yuugi takes over Yuugi's body and forces the opponent into a Shadow Game. The stakes are high as whoever loses shall have a taste of the darkness that resides within their own heart.