Although as a child he was very pious and wished to become a monk, his family sent him instead to the court of the Emperor Charles V. He distinguished himself there, accompanying the Emperor on several campaigns and marrying, in Madrid in September 1526, a Portuguese noblewoman, Eleanor de Castro Melo e Menezes, by whom he 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. In 1539, he convoyed the corpse of Empress Isabella of Portugal to her burial-place in Granada.
It is said that, when he saw the effect of death on the beautiful empress, he decided to "never again serve a mortal master." However, while still a young man, he was made viceroy of Catalonia, and administered the province with great efficiency. His true interests, however, lay elsewhere. When his father died, the new Duke of Gandia retired to his native place and led, with his wife and family, a life devoted entirely to Jesus Christ and The Holy Catholic Church.
In 1546 his wife Eleanor died and Francis was determined to enter the newly formed Society of Jesus. He put his affairs in order, renounced his titles in favour of his eldest son, Carlos, and became a Jesuit priest. Because of his high birth, great abilities and Europe-wide fame, he was immediately offered a cardinal's hat. This, however, he refused, preferring the life of an itinerant preacher. In time, however, his friends persuaded him to accept the leadership role that nature and circumstances had destined him for: in 1554, he became the Jesuits' commissary-general in Spain; and, in 1565, the third Father General or Superior General of the Society of Jesus.
His successes 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, dispatched missionaries to distant corners of the globe, 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.