The ancient Dominican Bishop, Rodrigo de la Peña— Inquisitor-General of Spain—has arrested a fellow priest and inquisitor, the Jesuit Enrique Mendoza, on the false charge of doctrinal heresy. Under the threat of incineration, de la Peña forces the younger man to alter his religious account—Historias Glorias— of the Conquest of Mexico to conform to de la Peña's far more secular and brutal recollections. As it turns out, de la Peña was himself a conquistador and has a remarkable story to tell.

Mendoza resists but gradually, inevitably, the old Bishop bends him to his will. De la Peña—always taunting and humiliating the terrified Mendoza—relates the details of his grim life. Orphaned by the Holy Office he enlists with Spanish mercenaries fighting in Italy. Surviving wounds and disease, he learns the art of combat and killing. Goaded by an oath to his dying father, he returns to Spain, intending to hunt down those who destroyed his family.

With authorities in hot pursuit Rodrigo flees to Cuba, joining a five hundred-man expedition under the—until then—unknown Hernán Cortés. The little little army sails for Mexico, fights battles against appalling odds, and receives incredible golden gifts from the Emperor Moctecuzoma.

The army is divided against itself, some loyal to Cortés and others more loyal to the Governor of Cuba, Don Diego Velasquez. Cortés, taking no chances, destroys his ships making retreat to Cuba virtually impossible. The army marches to the west, negotiating with or fighting the various tribes. They defeat the city state of Tlaxcala and perform an especially memorable butchery in the Mexican city of Cholula.

Gradually, Rodrigo and Cortés become estranged, partly because of competition for the affections of a beautiful Italian adventuress and partly for reasons of military strategy. Rodrigo prefers to attack Tenochtitlan from the shores of Lake Texcoco. Cortés prefers to enter Tenochtitlan, flatters Moctecuzoma, and subvert the empire. Cortés has his way.

Skull Rack ends with the tiny Castilian army on the heights overlooking Lake Texcoco. Tenochtitlan gleams in the distance.