During an eviction night on Big Brother, riots occur in several cities across the UK, with emergency services struggling to cope and the military being called in, and the live show may be bumped for related news. Producer Patrick tries to maintain control, issuing orders to the runners and his assistant Claire, while former seasons' housemates Aisleyne, Imogen, Helen, Bubble, Brian, Kinga, Eugene, Makosi and Ziggy are having a reunion party in the studio green room and presenter Davina McCall prepares for the post-eviction interview. The current housemates, Marky, Veronica, Grayson, Joplin, Angel, Space, and Pippa, get ready for eviction. Runner Kelly and co-worker Danny flirt in an outer office until co-worker Chloe interrupts, making frank accusations about Kelly and Danny's activities. Meanwhile, Kelly's boyfriend Riq is stranded at a railway station after his van is stolen. Another runner, Sophie, travels to the studio with Pippa's mother and their driver, who is bitten by a zombie on the way there. They reach the studio as he dies and reanimates, killing both women and biting a security guard. As Pippa's eviction is announced, the guard stumbles into the crowd of fans, dies, reanimates, and begins infecting others. The zombies invade the studio's interiors and attack Davina, the production crew, and the former contestants. Zombie Danny kills Chloe, but Kelly manages to barricade herself in an office and sees a news report of the zombie outbreak. Meanwhile, Patrick hides in a toilet cubicle after sacrificing Claire and a disabled man to save himself; then, he finds Pippa in the Big Brother green room while trying to escape from zombie Davina.

In the morning, the housemates are bickering, oblivious to the situation and wondering why Big Brother seems to ignore them, with only Space realising that something is wrong. Kelly kills Danny by stabbing him in the head with a knife. She is then chased outside and attempts to escape in a van. She gets the keys but is forced back inside the closed studio, where she escapes from a zombie cameraman lurking in the camera runs by entering the house via the Diary Room's fire exit door. Most of the housemates believe that she is a new contestant, and she tries to explain that there is a zombie outbreak and that something is behind the two-way mirrors, with Space the only one to believe her initially. Marky opens a door to taunt her, and the cameraman bursts into the house, biting Angel before Kelly smashes his head with a fire extinguisher.

Riq hides from zombies in a petrol station, where he is rescued by another survivor named Alex. The two set off for the coast in her car, which eventually breaks down. Riq attempts repairs while Alex stands guard, occasionally shooting approaching zombies. While Riq struggles to fix the car, Alex yells at him, angrily revealing that she had to shoot her zombified best friend dead to survive. The sound of them arguing attracts many zombies, forcing them to leave the car and escape on foot. They take shelter in an abandoned country house. Patrick and Pippa are stuck in the green room with no means of communication; they begin to argue as they try to defend themselves from zombie Davina as she prowls the corridor outside, making the occasional attempt to get in. The housemates move Angel to the greenhouse in the garden so that she is contained if she turns. Grayson, a nurse, explains that he needs proper medical supplies to help her. Kelly, Marky, and Space plan to use the van outside to fetch supplies from the nearby supermarket. Kelly tells Grayson to stab Angel in the head if she dies. Veronica and Joplin create a diversion, buying the others time to get to the van to which Kelly has the keys. Several zombies, including Claire, chase Kelly, Space and Marky, who barely manage to escape, though Marky injures his arm while leaping into the back of the van.

Kelly, Marky, and Space make it to the supermarket and gather supplies. When they are chased out of the store, two policemen looking for looters shoot the zombies. One of the cops is bitten and then shot by his colleague, who explains that those bitten die and turn quickly. Thinking the wound on Marky's arm is a bite, the policeman threatens to shoot him, refusing to believe that it is not. Kelly picks up the dead policeman's gun and shoots his partner in the leg. More zombies appear, and Kelly, Marky and Space escape in the van, leaving the wounded policeman to the zombies. Grayson tries to comfort Angel, but when she stops breathing, he hesitates to stab her, and she attacks. Veronica and Joplin, hearing the screams, run to the garden. Grayson stumbles out of the greenhouse clutching his neck, and zombie Angel chases after Veronica until Grayson pushes Angel into the pool just before he dies and then reanimates. Joplin and Veronica trap zombie Grayson with a bed cover, and Veronica stabs him in the head just as Kelly, Marky, and Space arrive. Seeing that Angel cannot escape the pool, they conclude that zombies have little intelligence. Kelly declares that the living will win the day because they can still reason, then fatally shoots Angel in the head with the policeman's gun. At the country house, Riq turns on the television and discovers the Big Brother live feed is still broadcasting on E4. Alex hears a French radio broadcast say that a rescue boat has just left, stranding them and any other survivors. Suddenly, Riq sees Kelly and the others on screen.

Riq decides he must get to Kelly and convinces Alex to leave the safety of the country house with him so they can make their way to the studio by boat along the river. Alex is bitten by a zombie while opening a lock gate. Knowing that she will turn, Alex hands Riq her axe, and he reluctantly kills her with it.

With Pippa's reluctant help, Patrick kills zombie Davina, and he and Pippa make it to the studio control room. Using the PA system, they communicate with the housemates and eventually join them in the Big Brother house. Patrick wants to leave the safety of the house and head for the coast, but Kelly shows him the crowd of zombies at the gates, preventing them from leaving the compound. Patrick suggests they cut up Grayson's remains to use as bait to distract the zombies while they escape in the van. Most of the housemates disagree, but Joplin and a reluctant Kelly allow him to do so. Riq makes it to the studio and approaches the Big Brother house, where Marky shoots the zombies inside the compound with the policeman's assault rifle. Marky spots Riq and starts to shoot at him, thinking he is a zombie.

Marky misses shooting Riq several times before Kelly recognises him and stops Marky from shooting. Once inside, Riq warns that Patrick's plan will not work as there are too many zombies. The housemates decide to stay in the house as long as possible and tie up a resistant Patrick, who later manages to turn Joplin against the others, comparing their situation to Big Brother's changing social-dynamics, and takes Kelly hostage while Joplin carries the bowl of bait. Everyone follows them outside, but in the struggle, the bait is dropped, and Patrick fatally shoots Riq. As a devastated Kelly tries to shoot Patrick in a rage, a traumatised Pippa runs back to the studio's offices, and Space follows. A panicked Joplin opens the gates and is devoured by the oncoming zombies. Kelly, Marky, Veronica and Patrick run for the house, but the zombies, including Saskia, rip Patrick apart.

Space makes it to the control room and communicates using the PA system. Zombies quickly fill the camera runs, and Kelly realises they will easily make it through the two-way glass and fire doors. She urges Space to open the Diary Room – zombie Aisleyne bites him. He opens the Diary Room door just after the zombies force their way into the house. Only Kelly makes it into the Diary Room; Marky and Veronica are eaten alive, and Space sees that Pippa is one of the zombies trying to get into the booth alongside her undead mother. Kelly congratulates Space on winning the series of Big Brother, and tells him to open the outside door to the fire exit so she can fight her way to the van. He refuses, knowing she is vastly outnumbered and will be killed until Kelly reminds him of the advice he gave her to face her fears and seize the day. He relents and opens the door.

The next morning, Joplin, Space, Marky, Veronica and Kelly are seen as zombies; Joplin, Marky and Veronica feast on human remains, Space stares blankly around the control room, and Kelly stares into a camera in the Big Brother house; her zombified stare is broadcast on the Big Brother live feed on multiple televisions in the United Kingdom.