Nick Clark wakes up in a heroin den and flees outside after he finds his friend eating a person. He gets hit by a car and is transported to a hospital. Madison Clark, her daughter Alicia and her husband Travis visit Nick, her son, at the hospital.
At the school where Madison works, Madison confiscates a knife from a student who is worried about news reports of a virus spreading around the country.
Nick tells Travis about the gruesome scene at the church. Travis checks out Nick’s story at the church and finds maggot-infested guts on the floor. When Nick escapes the hospital, Madison and Travis ask his high school friend, Calvin, for help finding Nick.
While driving home, Madison and Travis hear screams and gunshots on a highway off-ramp. The next day at school, teachers and students watch footage of the incident: A victim ravages an EMT worker then attacks police, resistant to gunfire. Amid reports of city-wide violence, school adjourns early.
Nick meets with Calvin, who is his dealer. Calvin tries to kill Nick for becoming a liability to his drug business, but Nick fights back and kills Calvin. Nick brings Madison and Travis to Calvin’s body. They’re attacked by undead Calvin and escape. They pick up Alicia at her boyfriend Matt’s house and discover that Matt is sick from a bite mark.
Nick goes into heroin withdrawal. Unable to reach a doctor, Madison retrieves confiscated OxyContin from her high school. The principal, who has turned, attacks her. She bashes his head in.
Travis goes to his ex-wife Liza’s house to look for their son, Chris. They find Chris at a mob protest against cops who shot an infected homeless man. As a riot breaks out, they take shelter in a barber shop owned by Daniel Salazar and his wife, Griselda, and daughter, Ofelia. As they flee the riots, a scaffolding topples onto Griselda, mangling her foot.
Madison, Nick and Alicia see an infected neighbor, Mr. Dawson, attack his wife then make his way toward their house. They run to the home of their neighbors, Susan and Patrick Tran, to get a shotgun. Travis and his group arrive home, where he’s attacked by Mr. Dawson. Daniel shoots Mr. Dawson with the shotgun that Madison brings back. Meanwhile Alicia narrowly escapes an infected Mrs. Tran.
Madison asks Liza to kill her if she ever becomes infected. “Don’t make Travis do it,” she says. “It would break him.” She tries to kill Mrs. Tran but is stopped by Travis, who argues that Mrs. Tran might still be saved. Mr. Tran arrives home from a trip and is nearly killed by Mrs. Tran before newly arrived soldiers swarm into the yard and kill her.
The military secures the neighborhood with a perimeter fence and implements a strict curfew. The commanding officer, Officer Moyers, tells residents that they are in one of 12 safe zones south of the San Gabriel Mountains. Travis befriends Moyers, who informally makes Travis his community liaison. After a neighbor, Doug, goes missing, Travis learns that Moyers took Doug into custody for having an emotional breakdown.
Chris discovers a distress signal emitting from a house outside the Safe Zone and relays the information to Travis and Madison. At Madison’s insistence, Travis tells Moyers about the distress signal. He later sees gunfire erupt at the house, putting an end to the signal. Meanwhile Madison sneaks outside the Safe Zone and finds that soldiers have been killing non-infected people.
Liza provides medical assistance to residents in the neighborhood. Dr. Exner, a government doctor, praises her nursing skills and asks for help treating residents in the community. Dr. Exner recommends Griselda undergo surgery at a nearby hospital. She also examines Nick after learning about his addiction from Liza.
Nick siphons morphine from a sick neighbor’s morphine drip. Madison furiously beats him after she realizes he has been lying to her.
Ofelia flirts with a soldier, Corporal Adams, who unsuccessfully tries to procure medicine for Griselda.
Soldiers arrive to take Griselda to the local command post for surgery. They also take Nick against his will and detain him in a cell with a prisoner named Strand.
Liza accompanies Dr. Exner to the command post to help treat patients. Dr. Exner explains that they euthanize anyone with bite marks as a precaution. When Griselda dies from septic shock, Liza shoots her through the head to prevent reanimation.
Daniel and Ofelia capture Adams and interrogate him about Griselda and Nick’s whereabouts. Daniel secretly tortures Adams into revealing that Griselda and Nick are at a command post two miles away and that the military is planning to evacuate the area at 9 a.m., at which point all detainees at the command post will be terminated. He also reveals that the military locked 2,000 civilians in a local arena after the people began turning.
Travis warns Moyers that the community will revolt if Nick, Liza and Griselda aren’t returned soon. Moyers capitulates and takes Travis to the command center with a team of soldiers. They abort the mission and return to the Safe Zone after losing soldiers to an infected attack.
Madison and Travis inform Alicia and Chris that they’re leaving immediately for the desert. Adams convinces Travis to let him go after telling Travis where to find his family at the command post.
Daniel leads the herd of infected from the arena straight into the command post. As mayhem breaks out, Travis and his group infiltrate the command post. An evacuation helicopter for Dr. Exner and her ward abandons the besieged post.
Nick and Strand escape their holding cell but become cornered by infected. Travis’ group rescues Nick and Strand with help from Liza. As they make their getaway, Adams tries to kill Daniel but accidentally shoots Ofelia. Travis brutally beats Adams.
The group takes refuge at Strand’s oceanside estate. Strand tells Nick he is planning to flee to a large boat moored in the ocean.
On the beach, Liza shows Madison a bite mark on her torso and asks Madison to shoot her. Travis discovers them and, after coming to terms with Liza’s fate, shoots Liza himself.