Leibowitz, who is the focus of this script, is a technician engaged in weapons development at the time of the nuclear war that destroyed all of American civilization, and the rest of the World. The natural reactions of the holocaust survivors is to turn upon all scientists, and upon all fragments of science, to destroy them for being responsible for the devastation which took place. However, Isaac Edward Leibowitz receives Papal permission to form the new monastic order of Albertus Magnus, whose role it is to save books and manuscripts from the "simpletons". The formation of his Order is successful, but Leibowitz himself is caught in the act of "book-legging", and he is martyred by simultaneous strangulation and burning.

In Fiat Homo ("Let there be Man"; in the year 2525, six hundred years after the Flame Deluge), relics of the founder of their Monastery, the Blessed Leibowitz, are discovered by chance in an ancient fall-out shelter by Brother Francis Gerard of Utah, a novice guided by the Pilgrim (the "Wandering Jew"), while he is fasting in the desert during Lent, and which are skillfully used by the Abbot of his Monastery to have the founder of its Order elevated to Sainthood. Sure of his religious life, Brother Francis returns back to the Abbey, informing the other novices of his experience, who improve and elaborate upon his original story, until a rumor circulates that the young novice actually met, in the guise of the Pilgrim, the Blessed Leibowitz himself. Francis is immediately summoned into the office of Abbot Arkos to deny the rumors, which threaten to undermine the chance of the patron of the Abbey for Sainthood. Science is dormant, asleep in the archives garnered by the Abbey of the Blessed Leibowitz. Without any power instruments, the scale of warfare is intimate: bows and arrows, and laying siege.

In Fiat Lux ("Let there be Light"; A.D. 3174), the books so carefully preserved by the followers of Leibowitz are finally read by a man who is capable of making some sense of them, as a scientific civilization once again begins to develop, and North America takes steps toward reunification. Thon Taddeo is seen re-inventing basic concepts of electricity with the doubtful aid of the Leibowitzian Memorabilia. Electricity is rediscovered, and by this new illumination numerous agents of an ambitious Prince examine the Memorabilia, making secret sketches of the fortifications of their Abbey, in order to capture it, and exploit its buried knowledge. It deals with the development of a new Renaissance, and the shifting of power from the Church into yet another secular state.

In Fiat Voluntas Tua ("Thy Will be Done"; A.D. 3781), progress of science makes a deadly full-circle back to rockets, satellites, and nuclear weapons. The Abbot of "Sanly Bowitts" once again finds himself dealing with problems of radiation, civilian casualties, and euthanasia. As the bombs begin to fall, another generation escapes with its books and children...