Eight years after the events of BioShock, the first prototype of the Big Daddies, Subject Delta, has been awakened by the Little Sister tied to him: Eleanor Lamb. Learning that he will enter a state of coma if he does not fulfil his natural connection to Eleanor, Delta fights his way through Rapture to find Eleanor and save her from her mother, Sophia Lamb, who is using the Little Sisters of Rapture to her own philosophical ends.

In this sequel to BioShock, players take the unique role of the first Big Daddy himself, Delta and struggle with both survival, exploration and the moral challenges that lie ahead as he fights to be reunited with Eleanor and save the Little Sisters from Sophia Lamb.