The Story of B is presented as a diary of the American first-person narrator and protagonist, Fr. Jared Osborne, a Roman Catholic priest of the Laurentian order. The Laurentians have traditionally made it their duty to be the first group to recognize the Antichrist. With this mission in mind, an esteemed member of the order, Fr. Bernard Lulfre, personally tasks Jared with investigating an itinerant American lecturer, Charles Atterley, who has gained notable attention in Europe and whose ideas the Laurentians consider a potential danger to humankind.
Although told that Atterley was last spotted in Austria, Jared is initially unable to track down the enigmatic preacher. Upon discovering that Atterley is more commonly known to the public as "B," Jared at last discovers him on a lecture circuit throughout major cities in Germany. Jared begins to attend each of B's speeches and takes verbatim notes that he faxes back to Lulfre. Ultimately pressed for a judgment on the possibility of B's being the Antichrist, Jared is driven to penetrate B's inner circle where he soon finds his religious foundations shaken to their core.
Jared meets with and soon gets to know B personally. Although B immediately understands that Jared is a potential threat to himself and his movement, he does not seem to be as suspicious of or cold toward Jared as are the rest of B's cohort, including B's closest companion, the extremely distrusting, lupus-stricken Shirin. Instead, B welcomes Jared and seems legitimately motivated to educate him, even presenting his teachings to Jared one-on-one. Among the tenets of B's philosophy are: an advocacy of new tribalism and the "Great Remembering"—which is his idea humanity has forgotten its hunter-gatherer history and should reclaim this forgotten knowledge that once steadily supported humanity's survival—as well as an opposition to "totalitarian agriculture," the style of agriculture whereby its practitioners destroy all competition and assume all resources are made only for their own use. Jared finds himself logically supporting these and others of B's ideas, though is unable to rationalize them in terms of his religious convictions.
On a train after one of B's lectures, Jared stumbles upon the murdered body of B who has apparently been shot dead in an empty car. B's group of close followers clearly suspects Jared or his organization to be responsible for the murder. To Jared's surprise, Shirin resumes B's lectures where he left off and claims that she is now B. Even more surprising, she begrudgingly continues to personally tutor Jared in B's philosophies, though she openly calls Jared stupid, not because he lacks the capacity to learn but because she has never seen a person "with so much mental equipment being put to so little use." Shirin's further teachings include the idea of a Law of Life, the concept that storytelling may be a genetic characteristic of humans, the promotion of animism, and the notion that totalitarian agriculture results in ecological imbalance and over-population, which themselves are rapidly leading to humankind's self-destruction. Jared begins to see how he cannot remain devout to his order and in agreement with B's teachings simultaneously.
The diary abruptly picks up when Jared regains consciousness after being involved in an explosion. In the hospital, Jared attempts to piece together his memories, chronicling that one of B's lecture theatres was bombed; Shirin and B's inner circle are presumably all dead. Flown back to the United States to recuperate, Jared eventually confronts Fr. Lulfre from whom he learns that the Laurentian order indeed authorized both B's assassination and the bombing of the theatre. Jared renounces his devotion to the order and returns hastily back to Europe, desperately searching for any information about possible survivors of the bombing and lamenting his lack of knowledge about the people he seeks out, for example, the fact that he never even learned Shirin's last name. Ultimately, though, Jared recalls that the theatre had an underground tunnel through which Shirin and the others might have escaped. Visiting the mouth of the tunnel, which is barricaded by wooden planks, Jared finds contact information engraved in the wood.
He is later reunited with Shirin and the others, and the memory comes flooding in that he warned them to flee moments before the explosion, thus saving their lives. A brief epilogue explains that Jared and Shirin plan to completely disappear from the public eye together; moments before Jared must leave to board a plane, he urges the spreading of B's philosophy and writes the final words of his diary: that Charles Atterley, Shirin, he, and the reader, too, are all B.