Inside a casino, during one of their heists, the group known as Phantom Thieves of Hearts is cornered by the police. Unable to escape, the leader of the group (the game's protagonist) is put under arrest, and goes into interrogation. Thus he begins to tell his story. After defending a woman from being harassed by a powerful politician, the 16-year-old protagonist is charged with assault and put on probation, which results in expulsion from his school. Following this, the protagonist is transferred to Shujin Academy in Tokyo, being forced to live at a coffee shop by the name of Cafe Leblanc, under the supervision of a friend of his parents, Sojiro Sakura. After going to school and making a couple of friends, is when the story truly starts.
Persona 5 se déroule à Tokyo, le joueur incarne un protagoniste silencieux après son transfert au lycée Shujin. Au cours de l'année scolaire, lui et d'autres étudiants vont éveiller leurs Persona et devenir des justiciers masqués surnommés les "voleurs Phantom of Hearts". Ils vont alors explorer un royaume surnaturel appelé "Palace" pour voler la corruption qui réside dans le cœur des adultes.