Yamata no Orochi appears as a special boss in Ueno's Kuchinawa Cave, summoned by connecting with all the plasma on the field and then killing the Onamuchi field boss. He also acts as the final boss of the Virtual Beach's Izumo island, as well as a regular Daily Mission boss for players over level 95. By offering golden sake, players are able to summon a stronger variation for a chance to obtain the ability to fuse him. He is a special triple fusion of Quetzalcoatl, Nidhoggr, and Raja Naga and learns a special fire affinity spin skill at level 98.
In Persona 4 The Animation, Yamata-no-Orochi represents the bond between Yu and his classmate Ai Ebihara. Like in the game, Yu fused the necessary Personas to summon it, where his power assisted Yu in the battles against Shadow Kanji and Shadow Mitsuo.
In the True Ending special, Yamata-no-Orochi was summoned to defend Yu against Yoshitune's attack, as well as bring a message of support for Yu from Ai.
Orochi is found in the Samsara Tunnels underneath Anahata. One of the doors to his chamber has been severely dented beyond operability and he remarks that his prey recently escaped before he could devour them. Not wanting to lose another meal, he immediately sets upon the party as they try reach the middle of the bridge in front of him.
Orochi is set apart from other bosses in that he gets 8 press turns per round and has a noticeable limit on his MP pool. He will respond immediately to -kaja and -nda spells with Dekaja and Dekunda, which will seriously cut into his MP. Once he runs out, he will stick to using Mad Rush every press turn unless he has enough MP to use MP Thief, which he will use to start another magic skill barrage if allowed. The Null Poison auto skill will protect the party from his Foul Breath attacks and Null Mute skill will prevent him from starting up another magic barrage.
After Orochi is defeated, the party can continue deeper into the tunnels and reach a seperate area of Ajna. In the upper floor hallway, a woman who was presumably the victim Orochi mentioned can be found but sadly she has passed away. The party will obtain the Red Ring key item upon examining her.