He was born in Almodóvar del Campo, in the modern-day Province of Ciudad Real, to Alfonso de Ávila, of Jewish converso descent, and Catalina Xixón (or Gijón), a wealthy and pious couple.

There he undertook the study of philosophy and theology, in which he was fortunate to have as his teacher the noted Dominican friar Domingo de Soto.

He therefore traveled to Seville to await departure for the Indies in January 1527 with the Dominican friar, Julián Garcés, appointed the first Bishop of Tlaxcala.

The archbishop saw in the young cleric a powerful instrument to stir up the faith in Andalusia, and after considerable persuasion Juan was induced to abandon his journey to America.

[5] John seems to have lived in the initial years after 1526 in a small house in Seville with another priest, probably Contreras, and disciples gathered around him, in a loosely structured fraternal life.

It was at the request of the younger sister of one of these disciples, Sancha Carrillo, that he began in 1527 to write the Audi, filia (Listen, Daughter), a work he continued expanding and editing until his death.

However, his strong pleas for reform and his denunciation of the behaviour of the aristocracy meant that he was denounced to the office of the Inquisition in Seville in 1531, and put in prison in the summer of 1532.

Likewise, during the years 1546 to 1555, John lived with about 20 disciples in Córdoba, making it seem that he intended to begin some kind of formal foundation of apostolic priests.

[17] During his homily, Pope Benedict said that John of Ávila was a "profound expert on the sacred Scriptures, he was gifted with an ardent missionary spirit.

He dedicated himself to preaching and to the more frequent practice of the sacraments, concentrating his commitment on improving the formation of candidates for the priesthood, of religious and of lay people, with a view to a fruitful reform of the Church".

[18] According to the Apostolic letter for the proclamation to Doctor of the Church, John of Ávila explained that "Christian spiritual life, as a participation in the life of the Blessed Trinity, begins with faith in the God who is Love, is grounded in God's goodness and mercy as expressed in the merits of Christ, and is wholly guided by the Spirit".

John of Ávila authored a "prayerful and sapiential" theology, based on the "primacy of Christ and of grace in relation to the love of God, for which he showed "a profound knowledge of the Bible", without setting forth a systematic synthesis.