Don Harris and his heterochromic wife Alice are holed up in a remote countryside cottage in England during the original outbreak of the Rage virus in Britain, and are preparing dinner for four other survivors there with them: the elderly Geoff and Sally, the cold and steely Jacob and the helpless Karen whose boyfriend abandoned the group. Don and Alice have two young children, who were saved from the outbreak in Britain by a school trip abroad. As the group all sit down and eat, they suddenly hear a young boy outside banging on the door and begging to be let in. Don reluctantly lets the boy into the cottage, and, while having food, the boy says that he is from the nearby town Sandford and has been fleeing from his infected parents and a horde of many other infected. While explaining this, the cottage suddenly comes under attack by the infected, who have followed the boy. On their first attack, Karen is infected and then killed by Don. While Don briefly holds off the infected getting in, the group flee and get separated into two: Alice and the boy flee upstairs, while Geoff, Sally and Jacob try to escape through the cottage barn. The infected break through even as Geoff stays behind to hold them off, and he and Sally are both overrun while Jacob escapes through the barn window. At the same time, Alice follows the terrified boy upstairs to try and save him, while Don follows to try and save her. Don tries to convince Alice to flee but she refuses to leave without the boy, and when the infected corner her and the boy in a bedroom, Don abandons his wife and the boy and flees the cottage by himself. With dozens of infected in hot pursuit, Don flees across the farmland to the river dock, where Jacob is attempting to escape by a motorboat. While Don gets into the motorboat and starts it up, Jacob falls into the river and is infected by the infected who have waded into the waters after the survivors, then killed by Don with the motorboat's propeller-blades. Don then escapes downriver from the infected, emerging as the sole survivor.
After the Rage outbreak destroys and wipes out Britain, over the following twenty-eight weeks, the infected die from starvation, and a US-led NATO force enters London and begins repatriating the city with Britons who escaped during the exodus of infected Britain in the outbreak. Among the military force that guard and protect London and its repatriated residents are wisecracking sniper Doyle, and his good friend helicopter pilot Flynn, as well as chief medical officer Scarlet Levy and operation leader General Stone, and Don Harris (who is caretaker of the fully-functional and fortified repatriation zone District One in London).
Among the latest repatriated arrivals to London are Don and Alice's children Tammy and Andy, and the admittance of children into District One without Scarlet's authorisation shocks and worries her. During the two kids' medical inspection, Scarlet notes that Andy has the same heterochromic green and brown eye colour his mother Alice did. Andy and Tammy are reunited with their father Don, who takes them to his luxurious District One penthouse. When the kids ask about what happened to their mother, Don tells them about the infected attack on the cottage during the pandemic, but lies that he saw the infected kill Alice.
The following night, Andy has a nightmare of Alice tearing her face off as Andy fears he'll forget his mother's face; so the next morning, Tammy decies to sneak out of District One with Andy to get a picture of Alice from their old home, though Doyle notices the two sneak out and alerts Flynn. In the ruined, unoccupied area of London, after taking a motorbike from an abandoned pizzeria, Tammy uses it to drive herself and Andy across an empty London to their old home, where the siblings grab a picture of Andy and Alice together and stay to collect their other lost old belongings at the house. While exploring the old Harris home alone, a shocked Andy finds Alice living in one of the rooms, physically and mentally dishevelled from her isolation but otherwise alive. The reunion is cut short when the US military, having been sent to bring Tammy and Andy back to District One, arrive and take them and Alice back to the green zone, where Alice is separated from the kids and the three are detained.
During medical inspection of Alice, Scarlet is about to do a blood test and is trying to ask Alice how she stayed alive out in the post-outbreak country, when she notices an old bite scar on Alice's arm and fears Alice may be infected. Meanwhile, Don goes to a detained Tammy and Andy to take them home, but the kids are furious with their father for lying to them about their mother's fate and demand to know the truth about what really happened. Guilty over abandoning his wife, Don leaves and slips past the military security to go to Alice in the isolation room.
