Returning from a Hong Kong business trip, Beth Emhoff (Gwyneth Paltrow) has a layover in Chicago to rendezvous with a former lover before returning to her family in suburban Minneapolis. She appears to have contracted a cold during her trip. Her six-year-old son from a previous marriage, Clark, also becomes symptomatic and is sent home from school. Beth's condition worsens and two days later she collapses with severe seizures. Her husband, Mitch (Matt Damon), rushes her to the hospital, but she dies of an unknown cause.
Mitch returns home and finds that Clark has also died from a similar infection. Mitch is put in isolation but seems to be immune to the disease. He is released and returns home to his teenaged daughter Jory, who had been living with Mitch's former wife and her husband and has decided to stay with Mitch since he's now all alone. They face decaying social order and rampant looting of stores and homes. Mitch is unsure if Jory has inherited his immunity and he struggles with the frustration of quarantine, his desire to protect his daughter and learning that his wife was cheating on him immediately prior to both her death and that of his stepson.
In Atlanta, representatives of the Department of Homeland Security meet with Dr. Ellis Cheever (Laurence Fishburne) of the CDC and express fears that the disease is a bio weapon intended to cause terror over the Thanksgiving weekend. Dr. Cheever dispatches Dr. Erin Mears (Kate Winslet), an Epidemic Intelligence Service officer, to Minneapolis to begin investigating. Mears traces the outbreak back to Emhoff while negotiating with local bureaucrats initially reluctant to commit resources for a proper public health response to the virus. Dr. Mears later becomes infected and dies.
At the CDC, Dr. Ally Hextall (Jennifer Ehle) determines the virus is a mix of genetic material from pig and bat viruses. Work on a cure stalls because scientists cannot discover a cell culture within which to grow the newly identified Meningoencephalitis Virus One (MEV-1).
UCSF professor Dr. Ian Sussman (Elliott Gould) violates orders from Cheever (relayed through Hextall) to destroy his samples, and identifies a usable MEV-1 cell culture using bat cells. Hextall uses the breakthrough to work on a vaccine. Other scientists determine the virus is spread by fomites, with a basic reproduction number of four when the virus mutates, with projections of one in twelve of the population being infected, and a 25-30% mortality rate.
Conspiracy theorist Alan Krumwiede (Jude Law) posts videos about the virus on his popular blog. In one video, he shows himself sick and later claims he recovered using a homeopathic cure derived from forsythia. In a panic, people seeking forsythia overwhelm pharmacies, spreading and accelerating the contagion as the infected come into contact with healthy people.
Krumwiede's claims attract national attention. During a television interview he discloses that Dr. Cheever had secretly informed friends and family to leave Chicago just before the city was quarantined. Cheever is then informed the government will investigate and may charge him for leaking information. Later it is revealed Krumwiede had faked being infected by the virus in an attempt to increase profits for shareholders in companies producing and selling forsythia. Krumwiede is arrested for conspiracy and securities fraud, only to walk free when his many supporters successfully raise funds to provide for his bail.
Using an attenuated virus Dr. Hextall identifies a possible vaccine. To cut out the lengthy time it would take to obtain informed consent from infected patients, Dr. Hextall inoculates herself with the experimental vaccine and immediately visits her gravely ill father, who has been infected with MEV-1. The doctor does not contract MEV-1 and the vaccine is declared a success.
The vaccine's production is rapidly increased, but due to limited production, the CDC awards vaccinations by lottery based on birth date. Inoculations take place for one full year until every survivor is vaccinated. First responders, doctors and others designated by the government are declared exempt from the lottery. Dr. Cheever gives his fast-tracked MEV-1 vaccination to the son of Roger (John Hawkes), a CDC janitor who had overheard Dr. Cheever's phone call warning his girlfriend to leave Chicago.
Dr. Leonora Orantes (Marion Cotillard), a WHO epidemiologist, travels to Hong Kong to follow the Beth Emhoff lead. She collaborates with Sun Feng (Chin Han) and other local epidemiologists and public health officials; they identify Emhoff as patient zero. As the virus spreads, Feng kidnaps Orantes to use her as leverage to obtain MEV-1 vaccine doses for his village. Orantes spends months living with the villagers until the vaccine is announced. Feng exchanges Orantes for the vaccine doses. Her colleague mentions that the exchanged doses were placebos and Orantes rushes away to warn them.
The death toll reached 2.5 million in the U.S. and 26 million worldwide. Dr. Hextall places samples of MEV-1 in cryogenic storage, alongside samples of H1N1 and SARS.
The source of the virus is revealed to viewers. A bulldozer (coincidently, operating for the company Emhoff works for) knocks down a palm tree disturbing some bats, with one finding shelter and food in a banana tree. That bat then flies over a pig pen, dropping a chunk of banana from its mouth, which is then eaten by a piglet. Chinese chefs later collect pigs from the pen and take them to a Hong Kong casino. A chef is called away from his preparations of a piglet, and casually wipes his hands on his apron. The chef then shakes hands with Beth Emhoff, giving her the mix of bat and pig viruses that makes her patient zero and the origin of the MEV-1 virus.
Who plays Dr. Ellis Cheever?
Laurence Fishburne