Plot Don (Robert Carlyle) and his wife Alice (Catherine McCormack) prepare dinner where they are living with an old couple and two other people who are the only survivors in a heavily reinforced cottage somewhere in rural, Rage virus–infected island of Great Britain. As they are taking their meal, they suddenly hear a young boy banging on the door begging to be let in. At first they argue not to open it due to the Rage virus' outbreak. Don opens the door to let the child inside, who says he is from Sandford and has been fleeing his parents who are now infected. Moments later, a pack of the infected discover the hideout and break in, quickly overwhelming the group. Alice refuses to leave without the boy; Don abandons Alice and escapes in a boat, emerging as the sole survivor.

Over the course of 28 weeks, the infected have all starved to death and Britain is declared relatively safe again, allowing for re-population. The re-construction of Britain begins. The process proceeds throughout the weeks.

An American-led NATO force, under the command of Brigadier General Stone (Idris Elba), begins repopulating the country with both old and new residents. The chief medical officer of District 1, Major Scarlet Ross (Rose Byrne), is surprised by the inclusion of the very young, amongst whom are Tammy (Imogen Poots) and Andy (Mackintosh Muggleton), Don and Alice's children who were in Spain during the initial outbreak.

At 12 years old, Andy is the youngest person in Britain, and during their subsequent medical inspection, Lima notes Andy's heterochromia, a trait he inherited from his mother. Andy and Tammy are subsequently admitted to District 1, a heavily-reinforced, fully functional section of London on the Isle of Dogs guarded by the United States Army, including a detachment from Delta acting as a rooftop unit observation team. With them are a sergeant, Doyle (Jeremy Renner), and an observation helicopter pilot Flynn (Harold Perrineau). The children are reunited with their father Don, who is now head caretaker of the district. Inside their new penthouse, Don tearfully recounts his escape, saying that Alice was killed by the infected, but misrepresents the truth, saying that he witnessed Alice's death, to hide the fact that he fled and abandoned her to her fate.

The very next day, the two children slip out of the safe zone to return to their old home, where Andy discovers Alice, disheveled but alive. Andy and Tammy are recaptured by the US Army while Alice is decontaminated. A blood test reveals that she is infected with the Rage virus, but displaying few symptoms, labeling her an asymptomatic carrier, as evidenced by her bloodied eye. Though Scarlet wants to keep Alice alive to seek a possible vaccine or cure, she is overruled by Stone, who wants Alice killed to prevent a possible further outbreak of Rage.

Don visits his children in a holding room, where they confront him about his version of Alice's death. He then makes an unauthorized visit to Alice in her isolation cell, using his caretaker passcard to bypass security, and asks for forgiveness, which she seemingly grants. But when they kiss, the Rage virus in her saliva immediately infects Don, much to Alice's horror. Now infected, he brutally kills her and goes on the prowl in District 1, attacking and infecting soldiers.

The outbreak forces the area into lockdown. All the civilians are quarantined in safe rooms, which Don forces his way into, and begins to infect the confined civilians. Scarlet manages to rescue Tammy from containment but Andy gets separated from the group. Doyle and the soldiers are ordered, at first, to shoot the infected, but the chaos escalates into "Code Red": a general extermination of the populace to prevent any possible spread of the Rage virus, after which everyone gets fired upon. Doyle, unable to bring himself to comply with the drastic order, abandons his post and escapes with Scarlet, the children and others through an underground tunnel. Stone then orders that District 1 be fire-bombed, killing the populace and causing massive devastation. Meanwhile, large numbers of the infected, including Don, escape the initialized bombardment, occupying the city.

Stopping to rendezvous with Flynn's helicopter at the derelict remains of Regent's Park, Scarlet informs Doyle that the key to curing infection is in the children, who may have the same immunity as their mother. Flynn arrives by helicopter to pick up Doyle, but refuses to take anyone else, stating that they would be blown out of the air if he attempts to break the Code Red protocol. Suddenly, one member of the group grabs on to the helicopter skids, screaming at Flynn to take him with him. Flynn attempts to shake him off the helicopter, sweeping over a horde of oncoming infected, killing them with the rotor blades, and dislodging the man.

Flynn tells Doyle to head to Wembley Stadium, and Doyle heads off with his group of civilians. The group breaks into an abandoned car to escape the infected and the clouds of chemical gas being vented into the city by the military. In the process of starting the car by pushing it, Doyle is killed by soldiers with flamethrowers. Scarlet drives into the London Underground to evade a pursuing Apache helicopter, where she, armed with Doyle's M4 rifle, and the children continue on foot. She tries to guide their way with the night vision mode on the rifle's optic. When they are separated, Scarlet is ambushed and killed by Don, who has followed them. Don attacks Andy and bites him. Tammy shoots Don and saves Andy from death, though he is infected with the Rage virus. Andy remains symptom-free like his mother, though his eye turns the same color as his mother's was after infection. The children continue to Wembley Stadium and are picked up by an at first reluctant Flynn, who flies them across the English Channel to France which Doyle instructed him to do. While flying, they see the incinerated District 1 and the remains of London. No one alive knows that Andy is a carrier of the virus.

Another 28 days pass. Someone calls for help over the radio of Flynn’s helicopter, which turns out to be abandoned. As people's screams are heard, a swarm of Infected are shown running through a subway exit. The horde was shown running toward the Eiffel Tower, revealing the Rage Virus to have spread to mainland Europe.