In September 1529, he married a Portuguese noblewoman in Madrid, Leonor de Castro Mello y Meneses. They had eight children: Carlos in 1530, Isabel in 1532, Juan in 1533, Álvaro circa 1535, Juana also circa 1535, Fernando in 1537, Dorotea in 1538, and Alfonso in 1539. Charles V appointed him Marquess of Lombay, master of the hounds, and equerry to the empress. In 1539, he convoyed the corpse of Isabella of Portugal, Philip II of Spain's mother, to her burial place in Granada. In that same year, he became Viceroy of Catalonia, replacing Fadrique de Portugal y Noroña, though he was only 29. He delighted above all in producing ecclesiastical compositions, and these display a remarkable contrapuntal style and bear witness to the skill of the composer, justifying indeed the assertion that, in the sixteenth century and prior to Palestrina, Borgia was one of the chief restorers of sacred music. In 1543 upon the death of his father, the 3rd Duke, Francis became the 4th Duke of Gandía. His diplomatic abilities came into question when his attempt to arrange a marriage between Prince Philip and the Princess of Portugal failed, thus ending an attempt to bring these two countries together and resulting in his retirement. By then 33 years old, he had retired to his native place and devoted himself to religious activities.
Jesuit priest
In 1546 his wife Eleanor died, and Francis then decided to enter the newly formed Society of Jesus, after making adequate provisions for his children. He put his affairs in order circa 1551, renounced his titles in favour of his eldest son Carlos de Borja-Aragon y de Castro-Melo, and became a Jesuit priest. He helped in the establishment of what is now the Gregorian University in Rome. Upon Francis’ return from a journey to Peru, Pope Julius III made known his intention to make him a cardinal. To prevent this, Borgia decided, in agreement with St. Ignatius, to leave the city secretly and go to the Basque Country, where it was thought he would be safe from the papal desires. He felt drawn to spend time in seclusion and prayer, but his administrative talents also made him a natural for other tasks. In time his friends persuaded him to accept the leadership role that nature and circumstances had destined him for: in 1554, he became the Jesuit commissary-general in Spain, where he founded a dozen colleges. After only two years, St. Francis was also given responsibility for missions in the East and West Indies. In 1565, he was elected the third "Father General" or Superior General of the Society of Jesus, after the death in January 1565 of Diego Laynez,. His successes during the period 1565–1572 have caused historians to describe Francis as the greatest General after Saint Ignatius. He founded the Collegium Romanum, which was to become the Gregorian University, advised kings and popes, and closely supervised all the affairs of the rapidly expanding order. Yet, despite the great power of his office, Francis led a humble life and was widely regarded in his own lifetime as a saint. Francis Borgia died in 1572.
Veneration
Francis Borgia died on 30 September 1572, in Rome. He was beatified in Madrid on 23 November 1624, by Pope Urban VIII. He was canonized nearly 35 years later on 20 June 1670, by Pope Clement X. His liturgical feast was inserted into the General Roman Calendar in 1688 for celebration on 10 October, the date then free from other celebrations that was closest to that of his death.