After 15-year old Jaden Yuki receives the Winged Kuriboh card from his hero, Yugi Muto, he joins the Duel Academy with the intention of becoming the next King of Games.

Duel Academy was created by Seto Kaiba (who is 28 at the time of Yu-Gi-Oh! GX, 18 at the time of Yu-Gi-Oh! Duel Monsters), who signed the deal some time after the events of Duel Monsters. The students are devided into 3 dormitories, Slifer Red, Ra Yellow and Obelisk Blue, Slifer Red being the lowest, Obelisk Blue being the highest. Jaden Yuki, due to the low score he got on his written exam, was dumped into Slifer Red, along with his friends, Syrus Truesdale, and Chumley Huffington.

In episode 50, Chumley Huffington graduated from the school after being held back several years, and went off to become a card designer for Industrial Illusions. Zane Truesdale, Syrus' brother, also graduated, and they were both replaced at the beginning of season two by two new first years, Tyranno Kenzan, and Aster Phoenix.

In Japan, Jaden (or Judai as he is called there) is currently nearing the end of his second year. In the American dubbed version, he is currently on summer vacation, and is expected to return for season two sometime in September.

The shift from the original series to GX is accompanied by the notion of modernization. Dueling technology has evolved, and cybernetics surface as a prevalent theme among monsters, either in totality (Cyber Dragons/Vehicroids), or enhancement through the addition of machinery (Cyber Girls/Dinosaurs/Tarot) to emphasize the replacement of the ancient with the futuristic. Furthermore, the displays that show monster stats and Life Points totals change from blue and gold print to digital readouts with color-coded energy bars for Life Points.

Yu-Gi-Oh! GX began airing in Japan on October 6th 2004, only to begin in America just over a year later, on October 10th 2005.