The nightmare starts at a Cambridge primate research laboratory, where animal rights activists ignore a scientist's warnings and release a caged chimpanzee. The chimp carries the Rage virus, a genetically modified pathogen, and violently attacks an activist, triggering an immediate outbreak.
Twenty-eight days later, Jim, a bicycle courier, wakes up from a coma in an empty London hospital after a road crash. He wanders the completely abandoned streets of London, finding empty landmarks, trash, and piles of money. Entering a church, he discovers piles of corpses and encounters infected humans with blood-red eyes who scream and charge at him. He is saved by two heavily armed survivors, Selena and Mark, who blow up a gas station to kill the attackers.
After Mark is bitten during an ambush and Selena ruthlessly executes him before he can turn, Jim and Selena join up with taxi driver Frank and his teenage daughter Hannah. They pick up a radio broadcast from soldiers near Manchester claiming to have a cure and a fortified sanctuary. Driving north in Frank's black cab, the group bonds like a makeshift family.
When they reach the deserted military blockade, a drop of infected crow's blood falls into Frank's eye. As he rapidly begins to turn, arriving soldiers shoot him dead in front of his screaming daughter. Major Henry West welcomes the remaining trio to a secure, barricaded country mansion. However, Jim soon discovers the soldiers' true plan: there is no infection cure. Major West promised his men women to stop them from deserting, intending to keep Selena and Hannah as sexual slaves.
When Jim resists, he is led into the woods to be executed alongside a sympathetic corporal. Jim escapes, returns through the rainy grounds, and unleashes pure psychological warfare on the outpost. He frees a chained infected soldier named Mailer, who tears through the ranks. Jim slaughters the remaining captors with animalistic brutality to rescue Selena and Hannah. Major West shoots Jim, but Hannah runs West down in the cab and leaves him to be torn apart by infected.
Another twenty-eight days later, Jim awakens in a quiet rural cottage in Cumbria, tended to by Selena and Hannah. Outside, infected across Britain have starved to death. Hearing a jet engine, the three lay out long sheets of red cloth on a green hillside to complete the letters of the word "HELLO". A Finnish reconnaissance jet spots the signal, confirming help has arrived.