Francis Xavier was born in the castle of Xavier, in the Kingdom of Navarre, on 7 April 1506 according to a family register. He was the youngest son of Juan de Jasso y Atondo, who belonged to a prosperous farming family and had acquired a doctorate in law at the University of Bologna,and later became privy counselor and finance minister to King John III of Navarre (Jean d'Albret). Francis' mother was Doña Maria de Azpilcueta y Aznárez, sole heiress of two noble Navarrese families. He was thus related to the great theologian and philosopher Martín de Azpilcueta. Notwithstanding different interpretations on his first language, no evidence suggests that Xavier's mother tongue was other than Basque, as stated by himself, and confirmed by the sociolinguistic environment of the time.

In 1512, Ferdinand, King of Aragon and regent of Castile, invaded Navarre, initiating a war that lasted over 18 years. Three years later, Francis' father died when Francis was only nine years old. In 1516, Francis's brothers participated in a failed Navarrese-French attempt to expel the Spanish invaders from the kingdom. The Spanish Governor, Cardinal Cisneros, confiscated the family lands, demolished the outer wall, the gates, and two towers of the family castle, and filled in the moat. In addition, the height of the keep was reduced by half. Only the family residence inside the castle was left. In 1522 one of Francis's brothers participated with 200 Navarrese nobles in dogged but failed resistance against the Castilian Count of Miranda in Amaiur, Baztan, the last Navarrese territorial position south of the Pyrenees.Until he left for studies in Paris in 1525, Francis' life was surrounded by this war, which ended with Spanish conquest of Navarre in 1530.In 1525, Francis went to study at the Collège Sainte-Barbe, University of Paris, where he would spend the next eleven years. In the early days he acquired some reputation as an athlete and a fine high-jumper.

In 1529, Francis shared lodgings with his friend Pierre Favre. A new student, Ignatius of Loyola, came to room with them. At 38, Ignatius was much older than Peter and Francis, who were both 23 at the time. Pierre was won over by Ignatius to become a priest, but Francis had aspirations of worldly advancement. At first Francis was not much taken with Ignatius. He regarded the new lodger as a joke and was sarcastic about his efforts to convert students. Only after Pierre left their lodgings to visit his family, when Ignatius was alone with the proud Navarrese, was he was able to slowly break down Francis's stubborn resistance. According to most biographies Ignatius is said to have posed the question: "What will it profit a man to gain the whole world, and lose his own soul?" However, according to James Broderick such method is not characteristic of Ignatius and there is no evidence that he employed it at all. In 1530 Francis received the degree of Master of Arts, and afterwards taught Aristotelian philosophy at Beauvais College, University of Paris. Church of Saint-Pierre de Montmartre, Paris. On 15 August 1534, seven students met in a crypt beneath the Church of Saint Denis (now Saint Pierre de Montmartre), in Montmartre outside Paris. They were Francis, Ignatius of Loyola, Alfonso Salmeron, Diego Laínez, Nicolás Bobadilla from Spain, Peter Faber from Savoy, and Simão Rodrigues from Portugal. They made private vows of poverty, chastity, and obedience to the Pope, and also vowed to go to the Holy Land to convert infidels. Francis began his study of theology in 1534 and was ordained on June 24, 1537. In 1539, after long discussions, Ignatius drew up a formula for a new monastic order, the Society of Jesus (the Jesuits). Ignatius's plan for the order was approved by Pope Paul III in 1540.

In 1540 King John of Portugal had Pedro Mascarenhas, Portuguese ambassador to the Vatican, request Jesuit missionaries to spread the faith in his new Indian possessions, where the king believed that Christian values were eroding among the Portuguese. After successive appeals to the Pope asking for missionaries for the East Indies under the Padroado agreement, John III was encouraged by Diogo de Gouveia, rector of the Collège Sainte-Barbe, to recruit the newly graduated youngsters that would establish the Society of Jesus. Loyola promptly appointed Nicholas Bobadilla and Simão Rodrigues. At the last moment, however, Bobadilla became seriously ill. With some hesitance and uneasiness, Ignatius asked Francis to go in Bobadilla's place. Thus, Xavier accidentally began his life as the first Jesuit missionary.

Leaving Rome on 15 March 1540, in the Ambassador's train, Francis took with him a breviary, a catechism, and De Institutione bene vivendi by Croatian humanist Marko Marulić, a Latin book that had become popular in the Counter-Reformation. According to a 1549 letter of F. Balthasar Gago in Goa, it was the only book that Francis read or studied. Francis reached Lisbon in June 1540 and four days after his arrival, he and Rodrigues were summoned to a private audience with the King and the Queen. Francis Xavier devoted much of his life to missions in Asia, mainly in four centers: Malacca, Amboina and Ternate, Japan, and China. His growing information about new places indicated to him that he had to go to what he understood were centers of influence for the whole region. China loomed large from his days in India. Japan was particularly attractive because of its culture. For him, these areas were interconnected; they could not be evangelized separately.

He left Lisbon on 7 April 1541, Xavier's thirty-fifth birthday, along with two other Jesuits and the new viceroy Martim Afonso de Sousa, on board the Santiago. As he departed, Francis was given a brief from the pope appointing him apostolic nuncio to the East. From August until March 1542 he remained in Portuguese Mozambique, and arrived in Goa, then capital of Portuguese India on 6 May 1542, thirteen months after leaving Lisbon. Following quickly on the great voyages of discovery, the Portuguese had established themselves at Goa thirty years earlier. Francis' primary mission, as ordered by King John III, was to restore Christianity among the Portuguese settlers. According to Teotonio R. DeSouza, recent critical accounts indicate that apart from the posted civil servants, "the great majority of those who were dispatched as "discoverers" were the riff-raff of Portuguese society, picked up from Portuguese jails." Nor did the soldiers, sailors, or merchants come to do missionary work, and Imperial policy permitted the outflow of disaffected nobility. Many of the arrivals formed liaisons with local women and adopted Indian culture. Missionaries often wrote against the "scandalous and undisciplined" behavior of their fellow Christians.

The Christian population had churches, clergy, and a bishop, but there were few preachers and no priests beyond the walls of Goa. Xavier decided that he must begin by instructing the Portuguese themselves, and gave much of his time to the teaching of children. The first five months he spent in preaching and ministering to the sick in the hospitals. After that, he walked through the streets ringing a bell to summon the children and servants to catechism. He was invited to head Saint Paul's College, a pioneer seminary for the education of secular priests, which became the first Jesuit headquarters in Asia. Xavier soon learned that along the Pearl Fishery Coast, which extends from Cape Comorin on the southern tip of India to the island of Manaar, off Ceylon (Sri Lanka), there was a Jāti of people called Paravas. Many of them had been baptized ten years before, merely to please the Portuguese, who had helped them against the Moors, but remained uninstructed in the faith. Accompanied by several native clerics from the seminary at Goa, he set sail for Cape Comorin in October 1542. First he set himself to learn the language of the Paravas; he taught those who had already been baptized, and preached to those who weren't. His efforts with the high-caste Brahmins remained unavailing.

He devoted almost three years to the work of preaching to the people of southern India and Ceylon, converting many. Many were the difficulties and hardships which Xavier had to encounter at this time, sometimes because the Portuguese soldiers, far from seconding his work, hampered it by their bad example and vicious habits. He built nearly 40 churches along the coast, including St. Stephen's Church, Kombuthurai, mentioned in his letters dated 1544. During this time, he was able to visit the tomb of St. Thomas the Apostle in Mylapore (now part of Madras (Chennai) then in Portuguese India). He set his sights eastward in 1545 and planned a missionary journey to Makassar on the island of Celebes (today's Indonesia). As the first Jesuit in India, Francis had difficulty achieving much success in his missionary trips. His successors, such as de Nobili, Matteo Ricci, and Beschi, attempted to convert the noblemen first as a means to influence more people, while Francis had initially interacted most with the lower classes (later though, in Japan, Francis changed tack by paying tribute to the Emperor and seeking an audience with him).

In late August 1552, the Santa Cruz reached the Chinese island of Shangchuan, 14 km away from the southern coast of mainland China, near Taishan, Guangdong, 200 km south-west of what later became Hong Kong. At this time, he was accompanied only by a Jesuit student, Álvaro Ferreira, a Chinese man called António, and a Malabar servant called Christopher. Around mid-November he sent a letter saying that a man had agreed to take him to the mainland in exchange for a large sum of money. Having sent back Álvaro Ferreira, he remained alone with António. He died at Shangchuan from a fever on 3 December 1552, while he was waiting for a boat that would agree to take him to mainland China.

He was first buried on a beach at Shangchuan Island, Taishan, Guangdong. His incorrupt body was taken from the island in February 1553 and was temporarily buried in St. Paul's church in Portuguese Malacca on 22 March 1553. An open grave in the church now marks the place of Xavier's burial. Pereira came back from Goa, removed the corpse shortly after 15 April 1553, and moved it to his house. On 11 December 1553, Xavier's body was shipped to Goa. The body is now in the Basilica of Bom Jesus in Goa, where it was placed in a glass container encased in a silver casket on 2 December 1637. This casket, constructed by Goan silversmiths between 1636 and 1637, was an exemplary blend of Italian and Indian aesthetic sensibilities.

There are 32 silver plates on all the four sides of the casket depicting different episodes from the life of the Saint:

• Francis lies on the ground with his arms and legs tied, but the chords break miraculously.
• Francis kisses the ulcer of a patient in a Venetian hospital.
• He is visited by St. Jerome as he lies ailing in the hospital of Vicenza.
• A vision about his future apostolate.
• A vision about his sister's prophecy about his fate.
• He saves the secretary of the Portuguese Ambassador while crossing the Alps.
• He lifts a sickman who dies after receiving communion but freed from fever.
• He baptises in Travancore.
• He resuscitates a boy who died in a well at Cape Comorin.
• He cures miraculously a man full of sores.
• He drives away the Badagas in Travancore.
• He resuscitates three persons: a man who was buried at Coulao; a boy about to be buried at Multao; and a child.
• He takes money from his empty pockets and gives to a Portuguese at Malyapore.
• A miraculous cure.
• A crab restores his crucifix which had fallen into the sea.
• He preaches in the island of Moro.
• He preaches in the sea of Malacca and announces the victory against the enemies.
• He converts a Portuguese soldier.
• He helps the dying Vicar of Malacca.
• Francis kneels down and on his shoulders there rests a child whom he restores to health.
• He goes from Amanguchi to Meaco walking.
• He cures a dumb and paralytic in Amanguchi.
• He cures a deaf Japanese.
• He prays in the ship during a storm.
• He baptizes three kings in Cochin.
• He cures a religious in the college of St. Paul.
• Due to the lack of water, he sweetens the sea water, during a voyage.
• The agony of Francis at Sancian.
• After his death he is seen by a lady according to his promise.
• The body dressed in sacerdotal vestments is exposed for public veneration.
• Francis levitates as he distributes communion in the College of St. Paul.
• The body is placed in a niche at Chaul with lighted candles. On the top of this casket there is a cross with two angels. One is holding a burning heart and the other a legend which says, "Satis est Domine, satis est." (It's enough Lord, it's enough)

The right forearm, which Xavier used to bless and baptize his converts, was detached by Superior General Claudio Acquaviva in 1614. It has been displayed since in a silver reliquary at the main Jesuit church in Rome, Il Gesù. Another of Xavier's arm bones was brought to Macau where it was kept in a silver reliquary. The relic was destined for Japan but religious persecution there persuaded the church to keep it in Macau's Cathedral of St. Paul. It was subsequently moved to St. Joseph's and in 1978 to the Chapel of St. Francis Xavier on Coloane Island. More recently the relic was moved to St. Joseph's Seminary and the Sacred Art Museum. In 2006, on the 500th anniversary of his birth, the Xavier Tomb Monument and Chapel on the Shangchuan Island, in ruins after years of neglect under communist rule in China was restored with the support from the alumni of Wah Yan College, a Jesuit high school in Hong Kong.