After travelling to New York City on a business trip, Russell Shoemaker wakes to find all electronic technology dead and more than 96.2% of the human race missing. Driven by a need to discover the truth and determined to return to his family, he embarks on a journey to his home in Seattle, while recording and telling all of the events in his journal. Afterworld is the story of Russell's 3,000-mile (4,800 km) trek across a post-apocalyptic America as he encounters the strange new societies rebuilding themselves. Along the way, he also attempts to solve the mystery of what caused this global event, which survivors refer to as "The Fall".
In addition to new forms of government, Russell discovers that technology has failed due to a persistent electromagnetic pulse, a product of a collection of satellite that was activated almost simultaneously to The Fall. An additional side effect of the EMP is the rapid mutation of many forms of life, including Shoemaker himself. He describes that his night-vision has improved dramatically, along with his endurance. Other examples are seen in cattle Russell happens across, which are dying of a previously unheard of flesh-eating disease.
Russell's journey eventually brings him to a nearly deserted San Francisco, and the headquarters of an organization known as the Parthia Group, who had developed a form of nano-technology, which identified humans with a particular genetic makeup.