The novel is framed around a series of interviews conducted by a fictionalized version of the author Max Brooks, author of The Zombie Survival Guide (known in-universe as the "Civilian Survival Guide"), as he travels the world a decade after the end of what is most commonly referred to as the "Zombie War."
The pandemic begins twenty years previously in the early 21st century, with the infection of a boy in a village in Dachang, China; the release of the virus, referred to as "Solanum" in The Zombie Survival Guide, is implied to have been caused by the construction of the Three Gorges Dam. The Politburo initially covers up the outbreak by engineering a military crisis with Taiwan to avoid appearing weak internationally. Still, thousands of infected quickly spread the virus outside of China through immigration, human trafficking, and the organ trade.
The virus spreads to Cape Town, South Africa, where the first major public outbreak occurs, leading to the virus initially being dubbed "African rabies." A Mossad agent publishes a report detailing the undead threat and recommending countermeasures, but Israel is the only country to take it seriously. The United States, in particular, is overconfident and distracted by an upcoming election, responding only by deploying small special operations teams to temporarily contain isolated outbreaks. Israel, meanwhile, responds by enacting a policy of voluntary quarantine in which it ceases occupying the Palestinian territories, evacuates Jerusalem, and constructs a wall along the demarcation line established in 1967. The government also offers asylum to any Palestinian living in the formerly occupied territories and any Palestinian whose family previously resided in Israel. These policies spark a civil war by enraging the Israeli religious right, though the uprising is eventually suppressed by the IDF. Worldwide, a widely marketed placebo vaccine named Phalanx creates a false sense of security. This period later becomes known as the "Great Denial."
The following spring, an unnamed journalist reveals the uselessness of Phalanx and the truth of Solanum, sparking a crisis later dubbed the "Great Panic" in which global order collapses, with rioting, breakdown of essential services, and indiscriminate culling of citizens killing more people than the zombies themselves. Russia forces a decimation of its military to end rampant mutinies. Ukraine uses VX gas on refugees and its own citizens in an attempt to weed out the infected. Iran and Pakistan destroy each other in a brief nuclear exchange over a refugee crisis. When the U.S. military stages a high-profile battle in Yonkers, New York, their conventional warfare tactics prove futile against the overwhelming horde of zombies, and the military is routed on live television. The catastrophe causes the U.S. president to suffer a nervous breakdown, resulting in the Vice President and his cabinet invoking Section 4 of the 25th Amendment and forcibly removing him from office.
Paul Redeker, a former intelligence consultant for the apartheid-era South African government, develops a drastic survival strategy that designates large groups of humans as unwitting bait, distracting the undead to give safe zones time to fortify themselves and build up resources; most countries go on to adopt the controversial plan. The U.S. government evacuates west of the Rocky Mountains and establishes a new capital in Honolulu, Hawaii. The International Space Station remains crewed by three astronauts who volunteer not to return to Earth; its commander observes miles-wide "mega swarms" of zombies stretching across Central Asia and the Great Plains. The fallout from the Iran–Pakistan War, as well as the millions of global fires sparked by the crisis, creates a nuclear winter. Knowing that zombies freeze solid in extreme cold, many ill-prepared North American civilians flee into the wilderness of northern Canada, where an estimated eleven million people die of disease, hypothermia, starvation, and cannibalism.
Four years later, during a United Nations conference held off the coast of Honolulu aboard the recommissioned USS Saratoga, the U.S. declares its intention to go on the offensive against the undead, inspiring other countries to follow suit. Determined to lead by example, the U.S. military reinvents itself to more effectively combat zombies as, without a vaccine, every last one must be destroyed to end the pandemic—automatic weapons and mechanized infantry are replaced by semi-automatic rifles and volley firing, and soldiers are retrained to target the head over the torso and maintain steady rates of fire. Troops are also equipped with body armor designed to protect from infection via zombie bites or bodily fluids. The United Kingdom constructs fortified, elevated motorways to enable more accessible travel throughout Great Britain while the hordes of undead are being cleared. A new martial art known as Mkunga Lalem, translating to "the Eel and the Sword," is invented specifically to fight zombies.
The contiguous United States is liberated three years after the Honolulu Conference. Global victory is declared after another two years upon the liberation of China, although the British military does not fully liberate London until three years after "Victory in China Day" due to its prioritization of low casualties. Russia, its armories badly depleted, is forced to heavily employ the use of outdated World War II-era equipment while waging a costly, brute-force two-front war. France, desiring to restore its national pride and reputation after its humiliating defeats in the Battle of France, the Battle of Điện Biên Phủ, and the Algerian War, prosecutes its campaign of the war more aggressively than its Western allies. The U.S. president dies, most likely from heart failure caused by extreme stress, toward the end of the war.
Ten years after Victory in China Day, the world is still heavily damaged but slowly recovering. Tens of millions of zombies remain active, mainly on the ocean floor, mountains above the snow line, and in arctic areas; the United Nations fields a large force to eliminate them. Iceland remains completely zombified, as its cold weather and lack of military made it the most vulnerable country to the undead. Following a religious revolution sparked by rampant suicide within the Russian army during the war, Russia has become an expansionist theonomy intent on annexing the former Soviet republics and has adopted a repopulation program under which the nation's few remaining fertile women are used as state broodmares.
North Korea remains quarantined as its entire population mysteriously vanished at the beginning of the pandemic, presumed to have fled into vast underground fallout shelters while remaining ignorant to the end of the zombie threat; fears that the population are now zombified have so far prevented reunification with South Korea. Cuba has become a capitalist democracy, possessing the world's largest GDP. Tibet has become independent from China and hosts Lhasa as the world's most populous city, while China has democratized following a second civil war sparked by the collapse of the Three Gorges Dam. Several new, unnamed countries have emerged due to wartime governments expelling convicts into infested zones, with many of these criminals surviving and going on to establish their own independent "fiefdoms."
The overall quality of human life has diminished, including shorter life expectancies, limited access to running water and electricity, and the resurgence of diseases like the Spanish flu. Many animals have gone extinct due to overhunting, pollution, or being killed by the undead. Fossil fuels are scarce, with petroleum from the Middle East becoming practically nonexistent after Saudi Arabia destroyed its oil reserves for unknown reasons during the war; sailboats have returned as the most common nautical vessels. Nevertheless, the majority of those who have survived have hope for the future, knowing that humanity faced the brink of extinction and won.
