After destroying the Umbrella Corporation's Headquarter in Tokyo, Alice(Milla Jovovich) heads to Arcadia, in Alaska, seeking for survivors and following the broadcasted message that offers security, safety, shelter, food and no epidemics. However, the place has no one but Claire Redfield(Ali Larter) that wears a strange device on her chest and has no recollections. Alice withdraws the electronic device and flies with Claire to Los Angeles, where she sees a group of survivors on the roof of a prison asking for help and under siege of the undead. They land on the roof and they learn with their leader Luther West(Boris Kodjoe) that Arcadia is actually a ship anchored nearby the harbor that has stopped broadcasting the message a couple of days before. Alice and Claire team up with the survivors and they decide to move to the vessel since the crowd of zombies is menacing their fortress. But first they release Claire's brother Chris Redfield(Wentworth Miller) that is imprisoned in a cell. But in their journey to Arcadia, they have to fight against the legion of undead and also against a treacherous survivor.