Yuugi Mutou is a naïve and lonely high school student who is fascinated by games. While staying with his grandfather, the owner of a game shop, he comes across an ancient Egyption relic known as the Millennium Puzzle. Rumored to grant any wish to those who solve the Puzzle, Yuugi becomes determined to solve it to wish for some friends. After years of struggling, Yuugi manages to complete the puzzle and mysteriously finds that his wish has been fulfilled. Meanwhile, a new card game known as Duel Monsters starts rising in popularity. In this game, players called duelists fight against each other with monsters by using magic and trap cards to foil their opponent's plans. Yuugi quickly becomes skilled at the game and lives a peaceful life with his newfound friends. However, Yuugi's peace is short-lived. The undefeated duelist and egocentric billionaire Seto Kaiba suddenly abducts Yuugi's grandfather, forcing him to duel against the rare Blue Eyes White Dragon'' card. Yuugi is thrown into a new world of fierce battles and the stakes continue to rise as dark forces interfere from the shadows. After unexpectedly defeating Kaiba with the help of his other self—the spirit of a nameless pharaoh—contained in the puzzle, he unofficially becomes the top duelist known as The King of Games. However, this new title will attract covetousness and Yuugi will have to use all his intelligence and willpower in order to protect what he holds the dearest to him.

In the world of Duel Monsters, a new generation of duelists await their turn to bid for the highest title: The King of Games. As an aspiring duelist, the happy-go-lucky Juudai Yuuki enrolls at the Duel Academy, a reputable institution tasked with nurturing these potential challengers. On his first day, however, Juudai's laid back and careless attitude causes him to arrive late to his entrance exam. There, he stumbles upon a familiar figure who entrusts him the Winged Kuriboh, a card which becomes Judai's new partner. Soon, he begins living as a duelist—but will destiny and darkness bend his reality into something beyond his imagination? Yu☆Gi☆Oh!: Duel Monsters GX follows the story of Juudai as he strives to fulfill his goal of becoming the next King of Games. As they are thrust into countless unprecedented circumstances, one thing is for sure for Juudai and his friends—there will never be a dull moment at the Duel Academy!

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.