The Destroyer is a massive, intergalactic menace being from another dimension, sealed within Pandora. It appears as a gargantuan, one-eyed beast with a massive mouth and several tentacles. The Eridians, at the cost of their entire civilization, imprisoned The Destroyer within the Vault thousands of years ago.
Rumors of a Vault on Pandora have attracted the Vault Hunters in order to obtain whatever riches lie inside the Vault, after Atlas opened one in Promethea. The Guardian Angel made telepathic contact with four Vault Hunters and helped guide them to the key parts. She also knew what lay hidden in the Vault, but did not tell them as they would stop searching if she did.
The Vault Hunters obtain three of the key pieces, but are duped by Patricia Tannis into finding a fourth, later revealed be a ruse by the Crimson Lance. Having obtained the whole key, the Crimson Lance made their way to the Vault, fighting numerous Guardians along the way, who had set up defensive perimeters. Despite their efforts, Commandant Steele reached the Vault and opened it, only to be impaled by a tentacle, revealed to be from the Destroyer itself. It quickly killed off her escorting troops before focusing on the Vault Hunters, but was ultimately defeated. To protect its reputation, the Crimson Lance then claimed the kill, blaming the Vault Hunters for releasing it.
In Borderlands: The Pre-Sequel, it is revealed that Jack obtained the Destroyer's eye after its death and used it to create a superweapon for the under-construction Helios Moonbase. Dubbed "The Eye of Helios", it was capable of destroying entire settlements and nearly led to the destruction of Pandora's moon Elpis when Colonel Zarpedon of Dahl's renegade Lost Legion stole control of Helios. The Eye was later destroyed as part of Moxxi's attempt to foil Jack's plan. A side quest involved the Vault Hunters retrieving the pieces of the Eye and attempting to reuse it, but ultimately failed, and the Eye was completely obliterated.
In Borderlands 3, it is revealed that Pandora itself is an Eridian prison designed for The Destroyer known as the Great Vault, with Elpis acting as the key. The Eridium that revealed itself shortly after the first defeat of the Destroyer is (from an Eridian glyph inside Carnivora) an integral part of that prison, with much of Pandora's upper crust being comprised of it. The Destroyer survived its encounter with the original Vault Hunters by retreating back into its prison, and now the Calypso Twins aim to harness its power merging with it through the use of their Siren powers. Should the Great Vault be opened, Pandora will be destroyed, and The Destroyer will continue burning its way through the universe. The Eridians willingly gave their lives to bait The Destroyer into the Great Vault, and were sealed inside by the ancient Siren Nyriad. Nyriad, in an Eridian glyph found in a side tunnel of the Destroyer's Rift, states that the Destroyer cannot be restrained forever - either it waits for its prison to weaken over time, or it waits for someone to weaken its prison for it, as in the case of the efforts of the first vault hunters and the Calypso twins.
- Main article: Destroy The Destroyer
- Some players have experienced a bug that caused The Destroyer to vanish from play when one player exited during the fight. Upon a restart of the game The Destroyer is absent, the mission checked as complete and the Vault Key unobtainable. This could have been caused by a game crash during the fight in some cases.
- On some occasions, the game may crash on kill for a character scoped in on The Destroyer, and the kill will not be counted.
- The Destroyer is very similar to the final boss of Gearbox Software's first game, the Half-Life expansion Opposing Force which went by the name of "Gene Worm".
- The Overseer, a Guardian that administrates the Eridian Trials, remarks that the release of The Destroyer has started an investigation to see who was ultimately responsible.