Jerome was born in Venice, the son of Angelo Emiliani and Eleonore Mauroceni. His father died when he was a teenager and Gerolamo ran away at the age of 15 to join the army. In 1508, he participated in the defense of Castelnuovo against the League of Cambray. He was appointed governor of a fortress in the mountains of Treviso, and while defending his post he was taken prisoner. He had not cared about God but he attributed his escape to the intercession of the Mother of God; and he made a pilgrimage to the shrine of Our Lady of Treviso, in fulfillment of a vow, and left his chains as an offering. He was then appointed podestà of Castelnuovo di Quero, but after a short time returned to Venice to supervise the education of his nephews. All his spare time was devoted to the study of theology and to works of charity. In the year of plague and famine, he seemed to be everywhere and showed his zeal, especially for the orphans, whose number had so greatly increased. Jerome began caring for the sick and feeding the hungry at his own expense. He rented a house for them near the church of St. Rose and, with the assistance of some pious laymen, ministered to their needs. To his charge was also committed the hospital for incurables, founded by St. Cajetan. In 1531 he went to Verona and induced the citizens to build a hospital; in Brescia, Bergamo, Milan and other places in northern Italy, he erected orphanages, for boys and for girls. At Bergamo, he also founded a hostel for repentant prostitutes.
Two priests, Alessandro Besuzio and Agostino Bariso, then joined him in his labors of charity, and in 1532 Gerolamo founded a religious society, the Congregation of Regular Clerics. The motherhouse was at Somasca, a secluded North Italian hamlet in the Comune of Vercurago between Milan and Bergamo, after which the members became known as Somaschi. In the Rule of this Society, Gerolamo stated the principal work of the community was the care of orphans, poor and sick, and demanded that dwellings, food and clothing would bear the mark of religious poverty. Devoted to the guardian angels, Emiliani entrusted the Company to the protection of the Virgin, the Holy Spirit and the Archangel Raphael. The Congregation was approved in 1540 by Pope Paul III, and the Order, which has as its official name "Clerici Regulares S. Majoli Papiae Congregationis Somaschae," spread throughout Italy. During an epidemic, Jerome was assisting the sick when he contracted the plague. He died in Somasca, February 8, 1537.