In the midst of prosperity, enjoyed with his gracious and cultured wife and three fine sons, Judah Leon, Isaac and Samuel, he was disturbed by the turn of affairs in Portugal. His patron, Alfonso V, died, and was succeeded by Don João II (1481–1495), a man in every way unlike his father—stronger of will, less kindly, and full of dissimulation. He had been crowned in his father's lifetime, and was not rejoiced when Alfonso, believed to be dead, suddenly re-appeared in Portugal. João II followed the tactics of his unscrupulous contemporary, Louis XI of France, in the endeavor to rid himself of the Portuguese grandees in order to create an absolute monarchy. His first victim was to be Duke Ferdinand of Braganza, of royal blood, almost as powerful and as highly considered as himself, and better beloved. Don João II was anxious to clear from his path this duke and his brothers, against whom he had a personal grudge. While flattering the Duke of Braganza, he had a letter set up against him, accusing him of a secret, traitorous understanding with the Spanish sovereigns, the truth of which has not to this day been satisfactorily ascertained. He arrested him with a Judas kiss, caused him to be tried as a traitor to his country, sent him to the block, and took possession of his estates and wealth (June, 1483). His brothers were forced to fly to avoid a like fate. Inasmuch as Isaac Abrabanel had lived in friendly relations with the Duke of Braganza and his brothers, King João chose to suspect him of having been implicated in the recent conspiracies. Enemies of the Jewish statesman did their best to strengthen these suspicions. The king sent a command for him to appear before him. Not suspecting any evil, Abrabanel was about to obey, when an unknown friend appeared, told him his life was in danger, and counseled him to hasty flight. Warned by the fate of the Duke of Braganza, Abrabanel followed the advice, and fled to Spain. The king sent mounted soldiery after him, but they could not overtake him, and he reached the Spanish border in safety. In a humble but manly letter he declared his innocence of the crime, and also the innocence of the Duke of Braganza. The suspicious tyrant gave no credence to the letter of defense, but caused Abrabanel's property to be confiscated, as also that of his son, Judah Leon, who was already following the profession of a physician. His wife and children, however, he permitted to remove to Castile.

In the city of Toledo, where he found refuge, Isaac Abrabanel was honorably received by the Jews, especially by the cultured. A circle of learned men and disciples gathered round the famous, innocently persecuted Jewish statesman. With the rabbi, Isaac Aboab, and with the chief tithe-collector, Abraham Senior, he formed a close friendship. The latter, it seems, at once took him into partnership in the collection of taxes. Abrabanel's conscience pricked him for having neglected the study of the Law in following state affairs and mammon, and he attributed his misfortunes to the just punishment of heaven. He at once began to write, at the earnest entreaty of his new friends, an exposition of the books of the earlier prophets, hitherto, on account of their apparent simplicity, neglected by commentators. As he had given thought to them before, he soon completed the work. Certainly, no one was better qualified than Abrabanel to expound historical biblical literature. In addition to knowledge of languages, he had experience of the world, and the insight into political problems and complications necessary for unraveling the Israelitish records.

He had the advantage over other expositors in using the Christian exegetical writings of Jerome, Nicholas de Lyra, and the baptized Paul of Burgos, and taking from them what was most valuable. Abrabanel, therefore, in these commentaries, shed light upon many obscure passages. They are conceived in a scholarly style, arranged systematically, and before each book appear a comprehensible preface and a table of contents, an arrangement copied from Christian commentators, and adroitly turned to account by him. Had Abrabanel not been so diffuse in style, and not had the habit of introducing each Scriptural chapter with superfluous questions, his dissertations would have been, or, at all events, would have deserved to be, more popular. Nor should he have gone beyond his province into philosophical inquiry. Abrabanel accepted the orthodox point of view of Nachmani and Chasdaï, merely supplementing them with commonplaces of his own. He was not tolerant enough to listen to a liberal view of Judaism and its doctrines, and accused the works of Albalag and Narboni of heresy, classing these inquirers with the unprincipled apostate, Abner-Alfonso, of Valladolid. He was no better pleased with Levi ben Gerson, because he had resorted to philosophical interpretations in many cases, and did not accept miracles unconditionally. Like the strictly orthodox Jews of his day, such as Joseph Jaabez, he was persuaded that the humiliations and persecutions suffered by the Jews of Spain were due to their heresy. Yet, did German Jews, wholly untouched by heretical philosophy, suffer less than their brethren in Spain? Only a brief time was granted to Abrabanel to pursue his favorite study; the author was once more compelled to become a statesman. When about to delineate Judæan and Israelite monarchs, he was summoned to the court of Ferdinand and Isabella to be intrusted with the care of their finances. The revenues seem to have prospered under his management, and during his eight years of office (March, 1484-March, 1492) nothing went wrong with them. He was very useful to the royal pair by reason of his wisdom and prudent counsel. Abrabanel himself relates that he grew rich in the king's service, and bought himself land and estates, and that from the court and the highest grandees he received great consideration and honor. He must have been indispensable, seeing that the Catholic sovereigns, under the very eyes of the malignant Torquemada, and in spite of canonical decrees and all the resolutions repeatedly laid down by the cortes forbidding Jews to hold office in the government, were compelled to intrust this Jewish minister of finance with the mainspring of political life! How many services Abrabanel did for his own people during his time of office, grateful memory could not preserve by reason of the storm of misfortunes which broke upon the Jews later; but in Castile, as he had been in Portugal, he was as a wall of protection to them. Lying and fearful accusations from their bitter foes, the Dominicans, were not wanting. At one time it was said that the Jews had shown disrespect to some cross; at another, that in the town of La Guardia they had stolen and crucified a Christian child. From this tissue of lies, Torquemada fabricated a case against the Jews, and condemned the supposed criminals to the stake. In Valencia they were declared to have made a similar attempt, but to have been interrupted in the deed (1488–1490). That the Castilian Jews did not suffer extinction for the succor they afforded the unfortunate Marranos, was certainly owing to Abrabanel.

Meantime began the war with Granada, so disastrous for the Moors and Jews, which lasted with intervals for ten years (1481–1491). To this the Jews had to contribute. A heavy impost was laid upon the community (Alfarda—Strangers' Tax), on which the royal treasurer, Villaris, insisted with the utmost strictness. The Jews were, so to say, made to bring the fagots to their own funeral pyre, and the people, adding insult to injury, mocked them. In the province of Granada, which by pride had brought about its own fall, there were many Jews, their numbers having been increased by the Marranos who had fled thither to avoid death at the stake. Their position was not enviable, for Spanish hatred of Jews was strongly implanted there; but their creed was not attacked, and their lives were not in constant peril. Isaac Hamon was physician in ordinary to one of the last kings of Granada, and enjoyed high favor at court. One day a quarrel arose in the streets of Granada, and the bystanders implored the disputants to leave off in the name of their prophet, but in vain. But when they were bidden to give over in the name of the royal physician, they yielded. This occurrence, which testified that Isaac Hamon was held in more respect by the populace than the prophet Mahomet, roused certain bigoted Mahometans to fall upon the Jews of Granada and butcher them. Only those escaped who found refuge in the royal castle. The Jewish physicians of Granada came to the resolution henceforth not to clothe themselves in silken garments, nor ride on horseback, in order to avoid exciting the envy of the Mahometans.

After long and bloody strife the beautiful city of Granada fell into the hands of the proud Spaniards. Frivolous Muley Abu-Abdallah (Boabdil), the last king, signed a secret treaty with Ferdinand and Isabella (25th November, 1491) to give up the town and its territory by a certain time. The conditions, seeing that independence was lost, were tolerably favorable. The Moors were to keep their religious freedom, their civil laws, their right to leave the country, and above all their manners and customs, and were only required to pay the taxes which hitherto they had paid the Moorish king. The renegades—that is to say, Christians who had adopted Islam, or, more properly speaking, the Moorish pseudo-Christians—who had fled from the Inquisition to Granada, and returned to Islam, were to remain unmolested. The Inquisition was not to claim jurisdiction over them. The Jews of the capital of Granada, of the Albaicin quarter, the suburbs and the Alpujarras, were included in the provisions of the treaty. They were to enjoy the same indulgences and the same rights, except that relapsed Marranos were to leave the city, only the first month after its surrender being the term allowed for emigration; those who stayed longer were to be handed over to the Inquisition. One noteworthy point, stipulated by the last Moorish king of Granada, was that no Jew should be set over the vanquished Moors as officer of justice, tax-gatherer, or commissioner. On January 2d, 1492, Ferdinand and Isabella, with their court, amid ringing of bells, and great pomp and circumstance, made their entry into Granada. The Mahometan kingdom of the Peninsula had vanished like a dream in an Arabian Nights' legend. The last prince, Muley Abu-Abdallah, cast one long sad farewell look, "with a last sigh," over the glory forever lost, and retired to the lands assigned to him in the Alpujarras, but, unable to overcome his dejection, he turned his steps towards Africa. After nearly eight hundred years the whole Pyrenean Peninsula again became Christian, as it had been in the time of the Visigoths. But heaven could not rejoice over this conquest, which delivered fresh human sacrifices to the lords of hell. The Jews were the first to experience the tragical effect of this conquest of Granada.

The war against the Mahometans of Granada, originally undertaken to punish attempts at encroachment and breach of faith, assumed the character of a crusade against unbelief, of a holy war for the exaltation of the cross and the spread of the Christian faith. Not only the bigoted queen and the unctuous king, but also many Spaniards were dragged by this conquest into raging fanaticism. Are the unbelieving Mahometans to be vanquished, and the still more unbelieving Jews to go free in the land? This question was too pertinent not to meet with an answer unfavorable to the Jews. The insistence of Torquemada and friends of his own way of thinking, that the Jews, who had long been a thorn in their flesh, should be expelled, at first met with indifference, soon began to receive more attention from the victors. Then came the consideration that owing to increased opulence, consequent on the booty acquired from the wealthy towns of conquered Granada, the Jews were no longer indispensable. Before the banner of the cross waved over Granada, Ferdinand and Isabella had contemplated the expulsion of the Jews. With this end in view, they had sent an embassy to Pope Innocent VII, stating that they were willing to banish the Jews from the country, if he, Christ's representative, the avenger of his death, set them the example; but even this abandoned pope, who had seven illegitimate sons and as many daughters, and who, soon after his accession to the papal chair, had broken a solemn oath, was opposed to the expulsion of the Jews. Meshullam, of Rome, having heard of the pope's refusal, with great joy announced to the Italian and Neapolitan communities that Innocent would not consent to the expulsion. The Spanish sovereigns decided on the banishment of the Jews without the pope's consent.

From the enchanted palace of the Alhambra there was suddenly issued by the "Catholic Sovereigns" a proclamation that, within four months, the Spanish Jews were to leave every portion of Castile, Aragon, Sicily and Sardinia under pain of death (March 31, 1492). They were at liberty to take their goods and chattels with them, but neither gold, silver, money, nor forbidden articles of export—only such things as it was permitted to export. This heartless cruelty Ferdinand and Isabella sought to vindicate before their own subjects and before foreign countries. The proclamation did not accuse the Jews of extravagant usury, of unduly enriching themselves, of sucking the marrow from the bones of the people, of insulting the host, or of crucifying Christian children—not one syllable was said of these things. But it set forth that the falling away of the new-Christians into "Jewish unbelief" was caused by their intercourse with Jews. The proclamation continued that long since it would have been proper to banish the Jews on account of their wily ways; but at first the sovereigns had tried clemency and mild means, banishing only the Jews of Andalusia, and punishing only the most guilty, in the hope that these steps would suffice. As, however, these had not prevented the Jews from continuing to pervert the new-Christians from the Catholic faith, nothing remained but for their majesties to exile those who had lured back to heresy the people who had indeed fallen away, but had repented and returned to holy Mother Church. Therefore had their majesties, in council with the princes of the church, grandees, and learned men, resolved to banish the Jews from their kingdom. No Christian, on pain of confiscation of his possessions, should, after the expiration of a certain term, give succor or shelter to Jews. The edict of Ferdinand and Isabella is good testimony for the Jews of Spain in those days, since no accusations could be brought against them but that they had remained faithful to their religion, and had sought to maintain their Marrano brethren in it. A legend relates that their majesties were embittered against the Jews, because the Infante had found the picture of a crucified Holy Child in an orange which a Jewish courtier had given him.

The long-dreaded blow had fallen. The Spanish Jews were to leave the country, round which the fibers of their hearts had grown, where lay the graves of their forefathers of at least fifteen hundred years, and towards whose greatness, wealth, and culture they had so largely contributed. The blow fell upon them like a thunderbolt. Abrabanel thought that he might be able to avert it by his influence. He presented himself before the king and queen, and offered enormous sums in the name of the Jews if the edict were removed. His Christian friends, eminent grandees, supported his efforts. Ferdinand, who took more interest in enriching his coffers than in the Catholic faith, was inclined to yield. Then the fanatical grand inquisitor, Torquemada, lifted up his voice. It is related that he took upon himself to rush into the presence of the king and queen, carrying the crucifix aloft, and uttering these winged words: "Judas Iscariot sold Christ for thirty pieces of silver; your highnesses are about to sell Him for 300,000 ducats. Here He is, take Him, and sell Him!" Then he left the hall. These words, or the influence of other ecclesiastics, had a strong effect upon Isabella. She resolved to abide by the edict, and, of bolder spirit than the king, contrived to keep alive his enmity against the Jews. Juan de Lucena, a member of the royal council of Aragon, as well as minister, was equally active in maintaining the edict. At the end of April heralds and trumpeters went through the whole country, proclaiming that the Jews were permitted to remain only till the end of July to set their affairs in order; whoever of them was found after that time on Spanish ground would suffer death.

Great as was the consternation of the Spanish Jews at having to tear themselves from the beloved land of their birth and the ashes of their forefathers, and go forth to an uncertain future in strange lands, among people whose speech they did not understand, who, perhaps, might be more unfriendly towards them than the Spanish Christians, they had to bestir themselves and make preparation for their exodus. At every step they realized that a yet more cruel fate awaited them. Had they been able, like the English Jews at the end of the thirteenth century, and the French a century later, to take their riches with them, they might have been able to provide some sort of miserable existence for themselves; but the Jewish capitalists were not permitted to take their money with them, they were compelled to accept bills of exchange for it. But Spain, on account of its dominant knightly and ecclesiastical element, had no places of exchange like those in Italy, where commercial notes were of value. Business on a large scale was in the hands, for the most part, of Jews and new-Christians, and the latter, from fear, had to keep away from their brethren in race. The Jews who owned land were forced to part with it at absurd prices, because no buyers applied, and they were obliged to beg the Christians for even the meanest thing in exchange. A contemporary, Andreas Bernaldez, pastor of Los Palacios, relates that the most magnificent houses and the most beautiful estates of the Jews were sold for a trifle. A house was bartered for an ass, and a vineyard for a piece of cloth or linen. Thus the riches of the Spanish Jews melted away, and could not help them in their day of need. In Aragon, Catalonia and Valencia, it was even worse with them. Torquemada, who on this occasion exceeded his former inhumanity, forbade the Christians to have any intercourse with them. In these provinces Ferdinand sequestrated their possessions, so that not only their debts, but also the claims which monasteries pretended to have upon them were paid. This fiendish plan he devised for the benefit of the church. The Jews would thereby be driven to despair, and turn to the cross for succor. Torquemada, therefore, imposed on the Dominicans the task of preaching Christianity everywhere, and of calling upon the Jews to receive baptism, and thus remain in the land. On the other side, the rabbis bade the people remain steadfast, accept their trials as tests of their firmness, and trust in God, who had been with them in so many days of trouble. The fiery eloquence of the rabbis was not necessary. Each one encouraged his neighbor to remain true and steadfast to the Jewish faith. "Let us be strong," so they said to each other, "for our religion, and for the Law of our fathers before our enemies and blasphemers. If they will let us live, we shall live; if they kill us, then shall we die. We will not desecrate the covenant of our God; our heart shall not fail us. We will go forth in the name of the Lord." If they had submitted to baptism, would they not have fallen into the power of the blood-stained Inquisition? The cross had lost its power of attraction even for lukewarm Jews, since they had seen upon what trivial pretexts members of their race were delivered over to the stake. One year before the proclamation of banishment was made, thirty-two new-Christians in Seville were bound living to the stake, sixteen were burned in effigy, and 625 sentenced to do penance. The Jews, moreover, were not ignorant of the false and deceitful ways in which Torquemada entrapped his victims. Many pseudo-Christians had fled from Seville, Cordova and Jaen, to Granada, where they had returned to the Jewish faith. After the conquest of the town, Torquemada proclaimed that if they came back to Mother Church, "whose arms are always open to embrace those who return to her with repentance and contrition," they would be treated with mildness, and in private, without onlookers, would receive absolution. A few allowed themselves to be charmed by this sweet voice, betook themselves to Toledo, and were pardoned—to a death of fire. Thus it came about that, in spite of the preaching of the Dominicans, and notwithstanding their indescribably terrible position, few Jews passed over to Christianity in the year of the expulsion from Spain. Among persons of note, only the rich tax-collector and chief rabbi, Abraham Senior, his son, and his son-in-law, Meïr, a rabbi, went over, with the two sons of the latter. It is said that they received baptism in desperation, because the queen, who did not want to lose her clever minister of finance, threatened heavier persecution of the departing Jews, if these did not submit. Great was the rejoicing at court over the baptism of Senior and his family. Their majesties themselves and the cardinal stood as sponsors. The newly-baptized all took the family name of Coronel, and their descendants filled some of the highest offices in the state.

Their common misfortune and suffering developed among the Spanish Jews in those last days before their exile deep brotherly affection and exalted sentiments, which, could they have lasted, would surely have borne good fruit. The rich, although their wealth had dwindled, divided it fraternally with the poor, allowing them to want for nothing, so that they should not fall into the hands of the church, and also paid the charges of their exodus. The aged rabbi, Isaac Aboab, the friend of Abrabanel, went with thirty Jews of rank to Portugal, to negotiate with King João II, for the settlement of the Jews in that country, or for their safe passage through it. They succeeded in making tolerably favorable conditions. The pain of leaving their passionately loved country could not be overcome. The nearer the day of departure came, the more were the hearts of the unhappy people wrung. The graves of their forefathers were dearer to them than all besides, and from these they found parting hardest. The Jews of the town of Vitoria gave to the community the Jewish cemetery and its appertaining grounds in perpetuity, on condition that it should never be encroached upon, nor planted over, and a deed to this effect was drawn up. The Jews of Segovia assembled three days before their exodus around the graves of their forefathers, mingling their tears with the dust, and melting the hearts of the Catholics with their grief. They tore up many of the tombstones to bear them away as memorial relics, or gave them to the Moors.