Former UN employee Gerry Lane (Brad Pitt), his wife Karin (Mireille Enos) and their two daughters wake and enjoy a family breakfast.
Gerry tells the youngest daughter he quit his job to spend more time with the family. On the TV is some news about strife and talk of martial law.
Later, they sit in heavy Philadelphia traffic when the city is attacked by a horde of zombies -- these attackers move very quickly, biting people and the bitten being turned very rapidly.
The Lanes are in a car crash during the panic stampede and Gerry notices it takes approximately twelve seconds for a bitten person to change.
As the chaos spreads, the Lanes escape from the city in a stolen RV trailer.
They stop near Newark, New Jersey at a store where Karin stocks up on whatever food she can scrounge and Gerry is able to find medication for his daughter's asthma.
His wife is attacked by looters -- Gerry shoots one of them and Karin is let go.
Deputy Secretary-General Thierry Umutoni (Fana Mokoena) - an old friend of Gerry's - calls and tells the family that he is sending a helicopter to rescue them, however it will take until the next morning to arrive.
They take refuge in an apartment complex in Newark.
The Lanes hide out in a small apartment with a Latino family. One of the children, a boy named Tomas, speaks English and translates for the Lanes.
Gerry, believing that the best chance of survival is to keep moving, is unable to convince Tomas' family to leave with them.
The Lanes creep through the mostly abandoned tenement trying to find the roof but the undead detect them and they are chased to the roof. They find Tomas on the way. When Gerry is attacked by several zombies, they spew blood on him.
Arriving on the roof, Gerry steps to the edge, ready to throw himself off if the blood spilled on his face makes him turn.
He doesn't and, after holding off another horde of the undead, the family boards the chopper and escapes.
The helicopter takes the Lanes to a U.S. Navy aircraft carrier off the coast of New York City, where a team of scientists and military personnel are analyzing the scope of the worldwide outbreak.
Thierry is waiting there for them and fixes them up with bunks. A virologist, Dr. Andrew Fassbach (Elyes Gabel), argues that the plague is a virus, whose origin must be found in order for a vaccine to be developed. Because of his expertise as a former UN investigator, Gerry is tasked with helping Fassbach find the outbreak's source.
Gerry reluctantly agrees to help, on given the word that his family will be safe, and is sent to Camp Humphreys, a military base in South Korea, where an email was received about 11 days prior that stated that the outbreak may have started there.
Moments after arriving at the base, Gerry's team is attacked by zombies. Fassbach is killed after accidentally shooting himself. After being rescued by the base's surviving personnel, Gerry learns that the zombies are attracted to noise. The soldiers on the base, lead by Captain Speke, explain that a Korean soldier had been out in the field doing research when he was attacked and turned.
His conversion took considerably more time than what had been witnessed more recently. The corpse of the infected man attacked the base doctor & both were incinerated. Speke tells Gerry how one of his men was able to stand in the middle of the infected people and not be attacked. When Gerry asks the soldier, who walks with a slight limp, how he injured his leg, the soldier tells him something's been bothering him lately.
Gerry talks to a Ex-CIA agent, Haffner (David Morse), who'd been arrested for selling arms to North Korea. He tells Gerry a chilling account of how the North Korea government was able to contain the outbreak by pulling the teeth of every citizen within a 24 hour period, giving citizens no way to infect each other through bites.
Haffner tells Gerry to go to Jerusalem, where the Israeli Mossad had established a safe zone just before the outbreak was officially acknowledged, implying Israel might have had prior knowledge of what was to come. To get the C130 refueled and Gerry aboard, the Speke's men ride in a fleet of bicycles to avoid making any noise. Gerry's satellite phone goes off when Karin tries to call him and the undead attack. The plane is refueled successfully and Gerry and the C130 pilot manage to escape.
In Jerusalem, Gerry meets Mossad leader Jurgen Warmbrunn (Ludi Boeken), who explains that the Mossad had months earlier intercepted communications from an Army General in India, who stated that Indian troops were fighting the "rakshasa", or "dead spirits". Warmbrunn also explains how the center of Jerusalem was walled in -- the wall is formidable, at least 50 feet high and refugees are being brought in to the quarantine zone, including non-Jews and Muslims.
While Gerry talks with Jurgen, a group of Muslim refugees begin to sing joyously at finding a safe zone to survive in. One of the women is able to find a microphone and the singing grows louder. The zombies outside begin to climb the protective wall forming a massive pile that eventually succeeds in entering the city. While fleeing, Gerry notices that an old man and an emaciated boy are ignored by the zombies.
A young Israeli woman, Segen (Daniella Kertesz), Gerry's escort, is bitten by a zombie. Gerry quickly amputates her hand to stop the spread of the infection, counting to 12 until he's sure that she won't turn. Gerry and Segen eventually manage to board a Belarus Airways airliner after Gerry's pilot panics and flies away.
Contacting Thierry, Gerry asks for the nearest WHO or CDC type lab, they are diverted to a WHO research facility in Cardiff, Wales. While in the air, a stowaway zombie is released from the cargo hold and attacks a flight attendant. She attacks the rest of the passengers.
The plane crashes near Cardiff after Gerry detonates a grenade to kill the zombies. Segen and Gerry proceed as the only apparent survivors of the crash, Gerry has been impaled by a chunk of metal. Segen finds him and they walk to Cardiff and find the WHO facility. Out of contact, the US Navy assumes he is dead and deports his family to Nova Scotia.