《游戏王ZEXAL》是《游戏王》系列的第4部作品，标题logo采用了全新的设计，继承将世界观中游戏卡片被称为“Duel Monster”的说法。该作品也是最后一部由原作者高桥和希参与主要角色及世界观设定的《游戏王》系列动画。
该作讲述精力旺盛的主人公九十九游马以勇于挑战的“一飞冲天啊，我！”作为口号，以成为决斗冠军的目标而努力奋战，同谜之生命体Astral一起收集“No.卡”并对抗多种强大敌人的故事。
先导爱知是一个性格羞涩的中学三年级学生。他的爱好是收集以奇幻世界CRAY星球作为舞台的卡牌游戏《Vanguard》的游戏卡牌。他最大的骄傲是拥有一枚稀有卡牌“Blaster Blade”。平淡无奇的日子里，爱知再次遇见了当年送给他这张卡牌的神秘男孩Toshiki。2人的重逢，不仅激发了爱知体内的神秘力量，更使他的生活发生了翻天覆地的变化。在与不同的VG战士的热血竞赛中，爱知与他们建立了深厚的友情。
VG 10周年纪念特别动画「卡片战斗先导者overDress」来玩吧，愉快的夜晚开始了！
故事的主人公巴辛是一个非常爱好“交换卡片游戏”的小学六年级生。现在上学的小学校园里，正流行着一个在全世界都受到欢迎的卡片游戏“battle spirits”（战斗精神）。有一天，巴辛意外地得到了一张“辉石”……用辉石的力量，可以将“战斗精神”卡片中的怪物“spirit”们召唤到现实生活中来互相战斗。从此巴辛有了召唤卡片的能力。知道在学校传言中所说的传说的X珍稀卡片是实际存在的巴辛，与同样拥有辉石的竞争者们一起，为了能够得到这张X卡，而展开了激烈的卡片战斗。
当集齐了所有的X卡片时，就能实现与传说中最强的王者战斗的愿望。究竟能够称雄全世界的最强王者、以及能够赢得究极的卡片战斗的人究竟会是谁呢？！
在与异界王决战后两年，“激突王”马神弹连夺多次比赛的冠军，成为一众玩家的憧憬对象，可是本人却因为没有强大的对手而感到空虚。在紫乃宫麻衣的引领下，弹前往了未来的地球。在那里，两年前遗留下来的异界魔族统治了大部分地方，弹为了将人类从魔族的统治下解放，需要集齐十二宫稀有卡。成为“人类的救世主”的弹能成功解放人类吗？
主人公阳升一是13岁的少年，他梦想成为“战斗之魂”卡片游戏的新世界冠军“霸王（Hero）”，因此向卡片战斗的世界发起了挑战。
Shunta, a boy who loves Battle Spirits, is led by a card and called to the “Spirits World” in another dimension. Eto, the priestess who summoned Shunta, warns of the Spirits World’s demise due to the evil God-King’s resurrection. In order to stop it, she says they must bring back together the twelve God-Kings for their powers. Joined by Yoku Albatrosa, a boy summoned from another dimension, Shunta is led by Eto on a journey to find the twelve God-Kings who are scattered throughout the world.
In a new era of Battle Spirits, cards are treasures scattered throughout space. Adventurers called Card Questers battle against each other seeking out more and more powerful cards. The extremely tenacious Card Quester Rei and his beloved little dragon Mugen take off into the vast panoramas of space, blasting through the stratosphere of wild stars in the Star Number One. Rei masters various ultimate attributes, and transforms according to attribute colors!
It is the year 2030, and the stage is the capital of Japan, Chou-Tokyo. Through "Buddyfight", humans have started cultural interactions with residents from other worlds called "Affinity Dimensions". Buddyfight is a game with selected humans as the "Buddyfighter", and residents from the other world as the partner (known as "Buddy Monster"). These battles have high significance and sometimes it is even used to decide the fate of a nation, and naturally there are those who seek to use the Buddy Monsters for evil purposes.
Two years have passed since the Mauve's uprising.
Gallet Revolt who has landed in Grand Lolo, following his battle with Vizarga has undergone great changes in his ideals. While in the "white world," Gallet meets a certain young man.
Meanwhile, Varte Parx, who rose as the leader of the Mauve, uses his aerial fortress to put pressure on the Unified Government. The confrontation between the Unified Government and Mauve continues to intensify.
Can Gallet change the future laid out in the Otherworld Records? The cogwheel of fate continues to rotate, and the world finally enters a time of change.
The series follows the adventure of Bearers of Light's Core that will shape the destiny of the world.
The year is 2661 CE. Ten years ago, Bashin Dan became the trigger that stopped the Earth from resetting itself. On the anniversary of this sacrifice, Barone and Clackey hold a conference, celebrating the union of Mazoku and humanity, and also Dan's feats.
However, beneath that peace, an organization named Cardinal Sign advocates for the subjugation of Mazoku and human supremacy. They resort to terrorist attacks, violence, and have somehow obtained the 12 Zodiac X-Rares which ought to have vanished together with Dan.
Amidst all this chaos, the bearers of the core's light feel a weird sensation, one that they've felt before. What could be the meaning of it, and what is the meaning behind the card that appeared within their decks, named "The Clash King's Miracle"?