The novel begins in 2016 and spans more than ninety years, as colonies of humans attempt to live in a world filled with superhuman creatures who are continually on the hunt for fresh blood.

Occasional use is made of reference material from 1,000 years after the outbreak, coming from "The Journal of Sara Fisher", sourced from a future "University of New South Wales, Indo-Australian Republic".

The virus, while causing hemorrhagic fever and death in those who initially contracted it, results in a boosting of the immune system and enhanced strength and agility in the current subjects.

The FBI agents responsible for recruiting the prisoners are ordered to collect six-year-old Amy Bellafonte from a convent and deliver her to Dr. Lear, the head of the project.

Of the inmates, the first and last recruited are depicted as being different from the others: Babcock, the original test subject, is stronger and appears to have developed psychic abilities, occasionally influencing his guards and cleaners; and Carter, who was convicted of a first-degree murder he did not commit.

Lacey is taken by Carter, as Wolgast and Amy escape to a mountain retreat where they live for several months, occasionally picking up news of the contagion spread throughout America.

Despite living reasonably comfortably in the mountain site, Wolgast eventually succumbs to radiation sickness when a nuclear device is detonated nearby—he assumes that the government is attempting to sterilize infected areas of the country—and Amy is left to fend for herself.

During a nighttime attack, Amy arrives at the gates of the camp, having previously met Peter Jaxon (one of the colony's senior figures) during a foraging expedition.

The Haven's residents, most under the mental influence of Babcock, "feed" him blood sacrifices in exchange for being left alone by the horde of virals at his disposal, referred to as "The Many" (as opposed to The Twelve).

During a botched attempt to kill Babcock during one of the monthly blood sacrifice rituals, sympathizers at the Haven enable the group to escape via railroad, and they arrive at a farmstead.

While waiting for Babcock to arrive, the group is attacked, resulting in Alicia ("Lish") becoming infected, and treated by Sara, Michael Fisher's sister and the former medic of the First Colony, with 1 of the 12 syringes of the modified serum.

The attacking virals all collapse and willingly wait for the sun to rise so they can die, in most cases leaving behind nothing but dust, proving the hive theory correct.

The group return to Theo and Maus at the farmstead, where the baby, named Caleb, has been born safely but they relay a strange story about being attacked by a viral and neither remembering killing it, though it has a shotgun blast through its chest.

Peter and Lish realize the dead viral is actually Maus's husband, Galen Strauss who was turned since she left the Colony and either sought her out or just happened upon them at the farm.

The group begins discussing the idea of using the rest of the modified serum to raise more super soldiers to fight Zero, but Amy throws them all into the fire, citing concerns about sharing her miserable curse with other people and losing humanity.

Amy, Peter, Michael, Greer and Lish, after months of walking, return to the First Colony only to find it deserted, with no sign of what happened or where the colonists may have gone.

The other group is able to meet up with the Texan Expeditionary force, and their remaining story is related through parts of Sara's diary—her last entry is at Roswell Base, and among comments about her own pregnancy she states that she can hear gunshots, and is going to investigate.

Numerous individuals help Amy along her journey, including Brad Wolgast, an FBI agent whose job it is to procure people to be part of an experiment in which participants are infected with the virus, and, decades later, Peter Jaxon, a young man who lives in a tenuously surviving colony.

[4] Publishers Weekly criticized Cronin's use of certain "tropes" of the genre, but added that "he manages to engage the reader with a sweeping epic style."

The Passage is the literary equivalent of a unicorn: a bonafide thriller that is sharply written, deeply humane, ablaze with big ideas, and absolutely impossible to put down.

[3] Jason Ensler directed the pilot; the show began shooting in metro Atlanta in the summer of 2018 and premiered in January 2019 on Fox.