Following the Doom Marine's success thwarting hell in Doom, Doom II: Hell on Earth, and Final Doom, a planetary policy is established to quarantine the UAC research installations with apocalyptic levels of radiation. For years, the installations stood motionless and abandoned, until a long forgotten satellite monitoring one of the installations, barely functioning due to years of being subjected to the high levels of radiation, sends a message back to Earth.
The message indicates that a single entity, with vast rejuvenation powers and masked by the extreme radiation levels, managed to escape detection. This entity was able to systematically alter decaying dead carnage back into corrupted living tissue, resurrecting the demons.
Being the only experienced survivor of the "DOOM" episodes, the Doom Marine is sent in alone to exterminate them. Later, he realizes the demons had planned for this, after he unknowingly allowed himself to be lured back into hell. Despite this, the demons are unable to defeat him, and with the Unmaker, he eventually battles to and kills the Mother Demon. The game ends with the Doom Marine, no longer capable of having a normal life following his encounters with hell, deciding to remain in hell forever to ensure no demon ever rises again. For some period of time, he eventually wind up in Sentinel Prime, which triggers the event of the soft reboot Doom (2016).