The movie begins with an introduction to a documentary called The Death of Death. The movie then shows a view from a cameraman and a news reporter, reporting on a murder of a local family. The reporter and newswoman chat while the ambulance crew load the deceased bodies. Suddenly, one of the bodies moves and an ambulance worker attempts to resuscitate the person^[who?] when they are bitten. Another zombie approaches the news crew and police open fire on them but are ineffective at killing the zombies. The news lady is bitten on the neck while the cameraman films. The scene cuts to a group of young film studies students from the University of Pittsburgh:

• Jason
• Ridley
• Francine
• Mary
• Debra
• Tony
• Gordo
• Eliot

who are in the woods making their own horror film about a mummy along with their faculty advisor, Andrew Maxwell, when they hear on the radio the news of apparent mass-rioting and mass murder. Soon, these reports include cannibalism and the fact that the recently deceased are inexplicably waking and walking.

Ridley and Francine decide to leave the group, while Jason, who wants to film the events documentary-style, heads to the dormitory of his girlfriend Debra Monahan. Debra shows surprisingly good sense when we first see her, because when she opens her door, she is armed with a heavy candlestick, as where most people in this type of film would just open the door. When she cannot contact her family they travel in Mary's RV to the house of Debra's parents in Scranton, Pennsylvania. While driving her RV, Mary sees a car accident and runs over a highway patrolman and three other zombies trying to escape from them. The group stops and, after running over an undead state trooper, and then having to endure Tony declaring that she just killed real, living people, Mary tries to commit suicide shooting herself in the head with a pistol. Her friends take her to a hospital where they realize that the dead are returning to life as zombies and they need to fight to survive while traveling to Debra's parents' house. On their way the fuel line of the RV is cut but they are assisted by a deaf Amish man named Samuel. The real surprise here is Tracy, who reveals that she is familiar with auto repair because of her father's profession. Just before escaping Samuel is bitten and takes his own life by stabbing himself with a scythe through his head, but also taking the zombie with him. They later pass a city and are stopped by an armed gang. They try to barter with the men, who are better armed and supplied. The men are survivors of the attack on their city; everyone else left. The leader is a member of the National Guard, and does not believe the military will help. They rest in the city for a while, and edit their videos. There is a small argument amongst Jason and Debra, who does not share his belief in the need for videos. Jason sees the recordings as a necessity to show the world what was really happening. His uploaded videos reach 72,000 hits in eight minutes. They also find out that Debra's family were camping for the extent of the crisis, and is just now on their way home. The National Guard survivors gear up after one of their members had a heart attack and dies, then goes missing. They mistakenly kill one of their own and the chase the zombie into the fuel supply area, killing it with a canister of Hydrochloric acid. The students resupply and leave for Debra's house. They get a video stream from Tokyo from a survivor until they lose signal. The radio towers have become unreliable. The only dependable source of information is from the internet, added by bloggers.

When they arrive at Debra's house they assume that her family are still missing but find the reanimated corpses of her mother and brother who they fight off. They escape the house and decide to travel back to Ridley's mansion. Members of the real National Guard stop and rob them. The leader of the unit enters the RV and forces Jason at point blank to turn off his camera while they rob the RV. They steal all but the weapons (the bow and a shotgun) and run off shooting their rifles in the air.

The group watches video feed from a zombie hunting group. The group enter a building and find an old couple, who warn them not to come in. The group enters anyway and one of their members is attacked by a zombie. They kill three of them then the three uninjured men debate over whether or not to kill the couple for not telling them about their family members. The injured member kills the old couple before taking his own life.

They arrive at Ridley's mansion to an unlocked front door and find it abandoned. A bookcase in the mansion opens to reveal a Panic Room where a delusional Ridley stumbles out. He brings the group on a grand tour and then explains that his father was the first to turn, followed by a few of the servants and his mother and that Francine was attacked by his butler. He invites Debra and Tony to follow him outside to where he buried his family and the servants. It turns out that he did not bury them, but just put them in the pool. Ridley locks the two in the pool room and runs away to the house where he transforms and begins to hunt the group. The professor hears the commotion and runs into the panic room with the shotgun. Ridley attacks Tracy and Jason at the RV, before Jason distracts Ridley long enough for Tracy to knock him out. She then runs to the RV and drives away, angry at Jason for filming rather than helping. Ridley travels back to the house and pushes another member of the group into a bathtub; this member becomes electrocuted. The survivors go back to the panic room for a while, but Ridley returns and infects Jason. The professor cuts through Ridley's head with a sword and then Debra shoots Jason. Debra watches the video on Jason's camera and sees his last message, about his happiness to be documenting the events, apparently filmed right before his attack. Debra decides to continue the video.

In the morning they awake to see the staff of the mansion who were in the pool have made their way out and were breaking into the mansion. The professor, Debra, and Tony lock themselves in the panic room. Inside Debra watches the last thing Jason downloaded. Two men had formed a zombie hunting group and had tied three zombies to trees as targets. The last one was a woman hanging from a tree by her hair. They shot her in the lower part of her head, allowing the rest of the body to fall without causing the brain to be destroyed; the eyes can clearly be seen to be still moving. After seeing this, Debra wonders whether people are worth saving.