In 199X, Tokyo was destroyed by ICBMs, resulting in a nuclear holocaust. Some people with foresight had built underground shelters and survived the Great Cataclysm, while demons began to rampage on the ground. People in the underground shelters still need to defend against demon invasion, and thus an organization called Devil Busters have formed. Around 20 years passed, and a new generation has grown up in the shelters...

In Giten Megami Tensei, you play as Ayato Katsuragi, a devil buster who was born and raised in the Hatsudai Shelter. Ayato joins the force after his parents are brutally murdered by demons. He passes the exam with his friend Yuuka Tachibana, the reincarnation of Ishtar. Later, the shelter is attacked by demons, Ayato is possessed, and Yuuka is killed by demons. She is divided into eight pieces and gives one to each of his comrades. Ayato escapes and swears to get the body parts back.

The story is structured somewhat episodically. Ayato joins with Rui Asuka, Tatsuya Hayasaka, Emi Kirishima, Yoshio Nishino, Isamu Yamase, Tetsuya Sonoda, Kouki Kamikawa, Kazumi Yamada, Sanshirou Souma, and Doctor Kusaka. Many end up dead at one point in the story.