Set a generation into the future, Yu-Gi-Oh! GX revolves around a boy named Jaden Yuki as he begins his life at Duel Academy, owned by Kaiba Corp. While running late for his entrance exams, Jaden bumps into Yugi Muto, the King of Games! Seeing a Duel Disk and deck, Yugi thinks he must be a duelist, Jaden confirms this as he says he's on his way for his entrance exams for the Duel Academy. Yugi decides to give him a Winged Kuriboh card, saying it is a lucky card, and he wishes Jaden luck on his exams as he runs off.

As Jaden enters the school, he befriends Alexis Rhodes, Syrus Truesdale, Bastion Misawa, Zane Truesdale, and Chazz Princeton. Together they experience many adventures while trying to stop evil from spreading!