He was born to a wealthy, noble family in Thessalonica around 347. Filled more and more with a yearning for God, he abandoned his worldly possessions and traveled to Egypt, living for five years as a monk at Sketis. From there he went to Palestine, where he lived for another five years in a cave in the Jordan desert. Suffering from a severe ailment, he was forced to move to Jerusalem; there he was suddenly and completely cured following a vision on Golgotha, in which he saw the Good Thief come down from the cross to lead him to Christ, who gave the Cross into his keeping.

Porphyrius took up the trade of a shoemaker in Jerusalem to provide for his few needs. His humility and charity became so well-known that the Bishop of Jerusalem ordained him to the priesthood at the age of forty-five, and made him Stavrophylax, keeper of the True Cross of the Savior — thus fulfilling Porphyrius' vision on Golgotha. Three years later, much against his will, he was elected Bishop of Gaza.

Throughout his episcopate he was persecuted by the pagans who still dominated the life of that city — though he was able to convert many of them by his own example of holiness, and by the many miracles that were wrought through his intercessions. Once, when the city was suffering from a long drought, the Saint gathered the city's Christians (who numbered no more than 280), told them to fast, and celebrated an all-night vigil. The next morning, as the Bishop and his entire flock went in procession through the city it began to rain. At this, 127 pagans were converted. When the pagans' violent attacks continued, Porphyrius appealed to the Emperor Arcadius for an edict closing of the pagan temples in Gaza. With the support of St John Chrysostom the edict was issued. When the Imperial representatives entered Gaza, accompanied by Bishop Porphyrius bearing the Cross, the statue of Aphrodite in the city's main temple shattered into pieces. Eight temples were destroyed, and a Church was built on the site of the largest. Hundreds of pagans embraced the Faith and, after instruction, were baptized by the Saint.

After twenty-five years as bishop, during which he had seen his see transformed from a small flock of beleaguered Christians into a Christian territory, Saint Porphyrius reposed in peace in 420.