At the beginning of the novel, the main character, Hiro Protagonist, discovers the name of a new pseudo-narcotic, "Snow Crash", being offered at an exclusive Metaverse nightclub. Hiro's friend and fellow hacker Da5id falls victim to Snow Crash's effects, which are apparently unique in that they are experienced in the Metaverse and also in the physical world. Hiro uses his computer hacking, sharp cognitive skills, and sword-fighting to uncover the mystery of "Snow Crash"; his pursuit takes the reader on a tour of the Sumerian culture, a fully instantiated anarcho-capitalist society, and a virtual meta-society patronized by financial, social, and intellectual elites. As the nature of Snow Crash is uncovered, Hiro finds that self-replicating strings of information can affect objects in a uniform manner even though they may be broadcast via diverse media, a realization that reinforces his chosen path in life.
The protagonist is the aptly named Hiro Protagonist, whose business card reads "Last of the freelance hackers and Greatest swordfighter in the world." When Hiro loses his job as a pizza delivery driver for the Mafia, he meets a streetwise fifteen-year-old girl nicknamed Y.T. (short for Yours Truly), who works as a skateboard Kourier (courier), and they decide to become partners in the intelligence business (selling data to the CIC, the for-profit organization that evolved from the CIA's merger with the Library of Congress).
The pair soon learn of a dangerous new drug called "Snow Crash" that is both a computer virus capable of infecting the machines of unwise hackers in the Metaverse and a crippling CNS virus in Reality. It is distributed by a network of Pentecostal churches via its infrastructure and belief system. As Hiro and Y.T. dig deeper (or are drawn in) they discover more about Snow Crash and its connection to ancient Sumerian culture, the fiber-optics monopolist L. Bob Rife, and his aircraft carrier of refugee boat people who speak in tongues. Also, both in the Metaverse and in Reality, they confront one of Rife's minions, an Aleut harpoon master named Raven whose motorcycle's sidecar packs a nuke wired to go off should Raven ever be killed. Raven has never forgiven the United States for the way they handled the Japanese invasion of the Aleutian Islands (see Aleutian Islands Campaign in World War II) or for the nuclear testing on Amchitka.
Hiro, at the prompting of his Catholic ex-girlfriend Juanita Marquez, a designer of facial expressions for avatars, begins to unravel the nature of this crisis. It relates back to the mythology of ancient Sumer, which Stephenson describes as speaking a very powerful ur-language. Sumerian is to modern "acquired languages" as assembly language is to high level programming languages: it affects the entity (be it human or computer) at a far lower and more basic level than does acquired/programming language. Sumerian is rooted in the brain stem and related to glossolalia, or "speaking in tongues"—a trait displayed by most of L. Bob Rife's convertees. Furthermore, Sumerian culture was ruled and controlled via "me", the human-readable equivalent of software which contains the rules and procedures for various activity (harvests, the baking of bread, etc.). The keepers of these important documents were priests referred to as en; some of them, like the god/semi-historical-figure Enki, could write new me, making them the equivalent of programmers or hackers.
As Stephenson describes it, one goddess/semi-historical figure, Asherah, took it upon herself to create a dangerous biolinguistic virus and infect humanity with it; this virus was stopped by Enki, who used his skills as a "neurolinguistic hacker" to create an inoculating "nam-shub" that would protect humanity by making it impossible to use and respond to the Sumerian tongue. This forced the creation of "acquired languages" and gave rise to the Biblical story of the Tower of Babel. Unfortunately, Asherah's meta-virus did not disappear entirely, as the "Cult of Asherah" continued to spread it by means of cult prostitutes and infected women breastfeeding orphaned infants; this weakened form of the virus is compared to herpes simplex. Furthermore, Rife has been sponsoring archaeological expeditions to the Sumerian city of Eridu, and has found enough information on the Sumerian tongue to reconstruct it and use it to work his will on humanity. He has also found the nam-shub of Enki, which he is protecting at all costs.
Hiro makes his way to Rife's Raft, a massive floating refugee encampment built around Rife's converted personal yacht, the former USS Enterprise aircraft carrier. Juanita has already infiltrated the Raft in order to learn neurolinguistic hacking and help overthrow Rife. Y.T. is captured by Rife's followers and is taken to the Raft, where she becomes sexually involved with Raven for a short time and is eventually taken hostage by Rife personally. While hostage, Y.T. delivers the nam-shub of Enki to Hiro, who together with Juanita uses it to save those infected by the virus. Hiro then accesses the Metaverse and foils Raven's attempt to widely disseminate the Snow Crash virus to a collection of the hacker elite. Meanwhile, Y.T. is brought to the mainland by Rife, where she escapes. Rife and Raven proceed to an airport; subsequently they are confronted by the owner of the Mafia Franchise, Uncle Enzo. A battle ensues: A critically wounded Enzo disarms Raven, while Rife is killed and his virus destroyed by Fido; a dog-sized cybernetic guard unit known as a "Rat Thing". Fido had been rescued by Y.T. previously and retained his memories of her. Accelerating beyond Mach 1, Fido propels himself into the engine of L. Bob Rife's plane, destroying the aircraft with Rife on board. The novel ends with Y.T. driving home with her mother, and with hints of a rekindled relationship between Hiro and Juanita.