Former UN employee Gerry Lane, his wife Karin and their two daughters, Rachel and Constance, sit in heavy Philadelphia traffic when the city is attacked by hordes of zombies. As the chaos spreads, the Lanes escape the city in a stolen RV and arrive at Newark, New Jersey. After stocking up on asthma medicine for Rachel at a chaotic supermarket pharmacy, they take refuge in an apartment unit, home to another couple with a young boy named Tommy. Deputy Secretary-General Thierry Umutoni—an old friend of Gerry's—calls and tells the family that he is sending a helicopter to rescue them.
The helicopter extracts the Lanes and Tommy (who followed them after he escaped his infected parents) from the building to a fleet of U.S. Navy vessels off the coast of New York City, where scientists and military personnel analyze the scope of the worldwide outbreaks. A virologist, Dr. Andrew Fassbach, 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. After being given the ultimatum of either assisting the investigation or having him and his family removed from the vessel, Gerry reluctantly agrees to help and is sent to Camp Humphreys, a military base in South Korea.
Moments after arriving at the base, Gerry's team is attacked by zombies. An armed Fassbach turns to head back up the ramp, but slips and falls, and thus accidentally shoots himself dead. After being rescued by the base's surviving personnel led by Captain Speke, Gerry learns that the zombies are attracted to noise and the only way to stop them is to shoot them in their heads. He also learns the base doctor was infected and started to spread the infection before being incinerated by a soldier with a lame leg who was ignored by the infected. A former CIA operative is a surviving prisoner at the base, tells Gerry to go to Jerusalem, where the Israeli Mossad have established a safe zone just before the outbreak was officially acknowledged, implying Israel might have had prior knowledge of what was to come. As Gerry and his team bike stealthily to the plane, Karin calls him through his satellite phone, activating a loud ringtone that attracts the zombies. The zombies attack and kill several of the soldiers, including the remaining SEALs who accompanied Gerry, and Captain Speke, who commits suicide to prevent himself from turning, while they cover Gerry and his pilot during the escape.
In Jerusalem, Gerry meets Director of Mossad Jurgen Warmbrunn, 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." With this knowledge, the city quarantined itself. Jurgen then takes Gerry to the gates of the walls that were built by the Israelis after quarantining the city. The Israelis are allowing any survivors in to seek refuge inside the city. However, due to the loud singing and celebrations of the refugees within, several zombie climb up the up wall and forms an ant army like that evantually succeded in entering inside the refuuge. Jurgen orders Gerry's escorts to accompany him to his airplane. During their escape, Gerry notices that Jugen and an emaciated boy were ignored by the zombies. While fighting the horde, Gerry's escort, an Israeli soldier who identifies herself only as "Segen" is bitten by a zombie. Gerry quickly amputates her hand to prevent from turning her into a zombie. Gerry and Segen are eventually forced to escape overun Israel on an airliner when Gerry's pilot panics and flies away as the Israel is left in chaos.
Contacting Thierry, the pilots are diverted and set course for a WHO research facility in Cardiff, Wales. While in the air, a stowaway zombie escapes into the main cabin and attacks the passengers. The plane crashes after Gerry detonates a grenade to blow out all the zombies, the damage causing the pilots to lose control. Believing that Gerry has perished in the crash, Karin, Rachel, Constance, and Tommy are removed from the vessel by the military, as they are no longer considered "essential personnel." Segen and Gerry proceed on foot as the only apparent survivors, although Gerry is critically injured after being impaled by aircraft debris in the crash. He loses consciousness upon arrival at the facility.
Three days later, Gerry awakens inside the main building of the facility and meets with the surviving staff. Gerry reveals a theory he has, based on the fact that the lame soldier, old man and the sickly boy were ignored: the infected do not bite people who are seriously injured or already terminally ill, since they would be unsuitable hosts for viral reproduction. To test the theory someone would need to be infected with a pathogen from the facility. However, the wing of the building in which the pathogens are stored was overrun by zombies after a doctor accidentally infected himself. Gerry decides to go get a pathogen regardless, while Segen and the lead WHO doctor accompany him for backup. They fight their way through the zombies, and although Gerry is separated from Segen and the doctor (who were forced to return to the main building), he reaches the pathogen vault. After getting cornered inside the vault by a lone zombie, Gerry's only course of action is to perform an impromptu test of his theory. He injects himself with an unknown bacterial sample and opens the vault door: the zombie ignores him and later the entire horde runs past him. After he makes it back to the safe main building, everyone rejoices at his theory's success, and they restock their supplies and journey to an extraction point.
Gerry returns to his family (who have adopted Tommy), now relocated off the ship and to a safe zone in Freeport, Nova Scotia. A "vaccine" derived from deadly pathogens is developed that acts as camouflage for the troops battling the infected, and fleeing survivors can now cross zombie-infested areas with ease to quarantine zones. Human offensives begin against the zombies, and hope is restored. Gerry comments, "This isn't the end. Not even close. Our war has just begun."
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