Yu☆Gi☆Oh! Arc-V centers around Yuuya Sakaki, a mysterious Entertainment Duelist known as "The Phantom" along with his three other personalities: Yuuto, Yuugo, and Yuuri. He was chased after by Leo Corporation for hacking into their Solid Vision with mass system and used it for his own purpose.

While on the run, he meets Yuzu Hiiragi, the daughter of the principal of Syu Zo Duel School that was on the verge of bankruptcy and tricked Yuuya into a contract to become a teacher at her school. However, before Yuuya could teach at the school, he first must find a card called Genesis Omega Dragon that said will determine the fate of the world that also connected to his scattered memories.

The story is set in alternate version of Miami City where Leo Corporation, run by its president Reiji Akaba, dominates most of Solid Vision system throughout the city. The spread of the company's Solid Vision with mass not only gave birth to "Action Duels" but also help improving the city in saving lives and repair damage in case of disaster, becoming a vital part of people's life.