After defeating a mysterious enemy, Yuuma Tsukumo, along with the help of Kaito Tenjou and Ryouga "Shark" Kamishiro, has thwarted the Barians' plans. However, Yuuma is still on a quest to retrieve the Number Cards to restore Astral's memories. The Seven Barian Emperors catch wind of Yuuma and Astral's endeavors and begin to collect the cards themselves to achieve their ultimate goal: destroying Astral's world in exchange for saving their own. Though only five of the emperors are present, they unanimously decide on annihilating Astral and Yuuma once and for all. Elsewhere, with their newfound powers of ZEXAL, Astral and Yuuma work to eliminate the enemy force that threatens Earth and the rest of the universe. Yu☆Gi☆Oh! Zexal Second unveils the mysteries and unpleasant surprises that lie in the wake of Yuuma's adversities. As Astral struggles to accept his past and the consequences it may have brought, will the gods continue to shower their fortune upon Yuuma on yet another perilous adventure?

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.

Action Duels, which allow duelists to soar and swing alongside their Duel Monsters, are taking the world by storm. Due to an evolutionary breakthrough, the "Solid Vision" system is now able to provide Duel Monsters with mass. Yuuya Sakaki is Yuusho Sakaki's son, the latter being the founder of You Show Duel School in Miami City. Yuusho insists that duels are not a tool of war, but rather are to bring smiles to people and thus introduced the concept of Entertainment Dueling. However, at the height of his fame, Yuusho disappears and fails to attend his duel with Strong Ishijima, the Action Duel champion. Although scarred by this sudden leave, Yuuya vows to become an Entertainment Duelist like his father. Several years later, in the midst of a battle with Strong Ishijima, Yuuya's desperation to win brings forth a miracle. His pendant begins glowing, turning his cards into Pendulum Cards, which enables him to perform a Pendulum Summon—a summoning method unknown to the world and himself—gaining him fame overnight. As a result, Reiji Akaba, CEO of Leo Corporation and founder of the elite Leo Duel School, starts producing new Pendulum Cards to incorporate Pendulum Summoning into the system. Thus, the mysteries that surround Pendulum Summoning and Yuuya's father start to unravel, and Yuuya learns bit by bit what it takes to become an Entertainment Duelist.

The world of Duel Monsters is once again evolving with the development of a network called Link Vrains and a new summoning mechanic introduced as Link Summoning. By using this cyberspace, duelists can now create their own avatars and duel their way to glory within a virtual reality. However, much like the real world, the digital world is not free from war, conflict, and mysteries. Years ago, a hacker organization known as the Knights of Hanoi unleashed an attack on Link Vrains. Led by the anonymous Revolver, their aim was to annihilate the artificial intelligence program known as the Cyberse. After a failed attempt, one of their targets, Ignis, managed to escape and hide the Cyberse somewhere in the network. Five years later, high school student Yuusaku Fujiki encounters a strange artificial intelligence program while dueling in Link Vrains. Under the guise of his avatar named Playmaker, Yuusaku and his partner in crime, Shouichi Kusanagi, decide to join forces with the peculiar existence. As he seeks the truth behind a mysterious incident of the past, Yuusaku battles against the Knights of Hanoi and SOL Technologies in a race that might alter the fate of the world.