One group of characters are World War II–era Allied codebreakers and tactical-deception operatives affiliated with the Government Code and Cypher School at Bletchley Park (UK), and disillusioned Axis military and intelligence figures.

The second narrative is set in the late 1990s, with characters that are (in part) descendants of those of the earlier time period, who employ cryptologic, telecom, and computer technology to build an underground data haven in the fictional Sultanate of Kinakuta.

Their goal is to facilitate anonymous Internet banking using electronic money and (later) digital gold currency, with a long-term objective to distribute Holocaust Education and Avoidance Pod (HEAP) media for instructing genocide-target populations on defensive warfare.

It features fictionalized characterizations of such historical figures as Alan Turing, Albert Einstein, Douglas MacArthur, Winston Churchill, Isoroku Yamamoto, Karl Dönitz, Hermann Göring, and Ronald Reagan, as well as some highly technical and detailed descriptions of modern cryptography and information security, with discussions of prime numbers, modular arithmetic, and Van Eck phreaking.

In 1942, Lawrence Pritchard Waterhouse, a young United States Navy code breaker and mathematical savant, is assigned to the newly formed joint British and American Detachment 2702.

At the same time, Japanese soldiers, including mining engineer Goto Dengo, a "friendly enemy" of Shaftoe's, are assigned to build a mysterious bunker in the mountains in the Philippines as part of what turns out to be a literal suicide mission.

Circa 1997, Randy Waterhouse (Lawrence's grandson) joins his old role-playing game companion Avi Halaby in a new startup, providing Pinoy-grams (inexpensive, non-real-time video messages) to migrant Filipinos via new fiber-optic cables.

Several pages are spent explaining in detail some of the concepts behind cryptography and data storage security, including a description of Van Eck phreaking.

Stephenson's subsequent work, a trio of novels dubbed The Baroque Cycle, provides part of the deep backstory to the characters and events featured in Cryptonomicon.

Set in the late 17th and early 18th centuries, the novels feature ancestors of several characters in Cryptonomicon, as well as events and objects which affect the action of the later-set book.