Borderlands begins approximately 200 years after the discovery of the Vault; seeking the Vault, several fortune seekers, including the player, are drawn to Pandora. After arriving at the town of Fyrestone, the player sees an image of a mysterious woman, the "Guardian Angel", aware they are here to seek the Vault, and directs them to follow her instructions. The Angel eventually leads them to collecting one of the several artifacts needed to open the vault, causing Patricia Tannis, an archaeologist/scientist, to contact the player and urging them to collect the other two Vault keys, at the same time revealing that the Vault opens every 200 years, and the time of the next opening is approaching. At the same time, Commandant Steele of the Crimson Lance, a well-outfitted mercenary force in the employ of one of the game's several mega-corporations, threatens to declare martial law over the planet and demands the vault keys.
While the player is able to secure the second and third Vault keys without incident, they find that the final vault key is not where it is expected. Steele contacts the players, and reveals that Tannis had betrayed them, that there are in fact only three keys, and proceeds to cut off the planet's ECHO network, disabling further communication with the Guardian Angel. The player infiltrates the Crimson Lance's headquarters and finds Tannis locked up; she claims she had no choice but to betray the player under force, but urges him/her to restart the ECHO network and to prevent Steele and the Crimson Lance from using the key. After restoring the network, the Guardian Angel urges the players to hurry and stop Steele. The player finds as they approach the Vault that the Crimson Lance are in combat with alien Guardians; after bypassing both forces, the player finally arrives at the Vault, too late to stop Steele from using the key. However, when the Vault opens, Steele and her guard are wiped out by a giant monster that is attempting to escape the vault. The Guardian Angel explains that the monster is called the Destroyer, imprisoned in the Vault by the alien Eridians long ago to prevent it from destroying the universe, with the Guardians present to prevent anyone from opening it. The player is able to defeat the monster, sealing the Vault for another 200 years.
The final cut-scene reveals that the Guardian Angel is actually a Hyperion satellite in orbit over Pandora. In addition, the Claptrap at the beginning level suddenly shorts out, its normal blue eyelight turning red, and reveals its identity as an interplanetary ninja assassin.