The first season intertwines narratives from 2077 and 2296. In 2077, actor Cooper Howard becomes a Vault-Tec spokesperson before a nuclear war devastates Los Angeles. By 2296, Lucy MacLean, a resident of Vault 33, ventures into the treacherous wasteland to rescue her father, Hank, who was abducted by raiders. Throughout her journey, Lucy encounters various factions, including the Brotherhood of Steel and enigmatic figures like The Ghoul. The season delves into Vault-Tec's concealed experiments, the origins of the nuclear conflict, and the complex dynamics among survivors in a post-apocalyptic world.