The story takes place one year after the events of Resident Evil 4. Claire Redfield is now a member of Terra-Save, an organization which handles search and rescue at chemical and biological attacks. Claire arrives at Harvardville Airport to meet a friend.
A passenger airplane is approaching the airport to land. As one of the attendants checks the passengers, she notices one man looking unwell. The man in question is clearly in the final stages of T-virus infection, and warns the attendant. Shortly after, he zombifies.
Claire is looking after her friend's niece, Rani Chawla, when they see Senator Ron Davis walk by. While a zombie-masked protester is arrested by a police officer, another "zombie" comes along. The officer walks behind it to pull the mask off, but it is not a mask. He is bitten by the zombie. One of Davis' bodyguards shoots it. While surprised that the creature gets back up, he is attacked by the security guard, whom he thought was dead. The second guard attempts to run but is also devoured. The scene causes massive panic and people in the vicinity flee, some being attacked by more zombies, and the plane crashes into the building, with all of the occupants already transformed into zombies. Claire, Davis and Rani hide in the VIP lounge.