He was born in Rome, and as a young man was chosen by the Emperor Constantine to assist in the foundation of his new capital at Byzantium. An outbreak of leprosy in the new City became so severe that the Emperor ordered that all lepers, whatever their rank, be driven from the city or drowned in the sea. Zoticus, moved by compassion for these people, went to the Emperor and asked him for a large amount of gold to buy gems and pearls to enhance the glory of the city, 'For, as Your Majesty knows, I am well-qualified in this field.' The Saint then used the gold to ransom all those being led into exile or to drowning, and to establish for them a camp on the hill of Olivet on the opposite shore of the Bosphorus. There he brought the sick and provided for their care.

In 337 Constantius, an Arian heretic, took the throne upon the death of his father. Some of Zoticus' enemies at court, seeing an opportunity, denounced Zoticus to the new Emperor, saying that he not only held subversive views, but had misappropriated public money. When he learned of these charges, Zoticus presented himself to the Emperor, finely dressed, and offered to take Constantius to see the gems and pearls that he had bought on his behalf. When they reached the hill of Olivet, Constantius was astonished to see a company of lepers coming to greet him with lighted candles, honoring and praising him and their patron Zoticus. Then the holy Zoticus said to the Emperor, 'These are the precious stones and brilliant pearls that give luster to the crown of the heavenly Kingdom that you will inherit by their prayers. I bought them for the salvation of your soul.'

Instead of being grateful, the heartless Emperor ordered that Zoticus be tied behind wild mules and dragged until dead. The mules ran down the hill, breaking the Saint's body upon the rocks an brush. Then, of their own accord, they returned to the top of the hill, still dragging the body, and, like Balaam's ass (Numbers ch. 22), spoke and proclaimed that the Martyr must be buried on that hill. The astonished and repentant Emperor ordered the Martyr buried with honor, and commanded that a hospital for lepers be built there, staffed by the best physicians and caretakers.

Saint Zoticus is also called Orphanotrophos, 'Cherisher of Orphans,' because in later years a large orphanage was added to the leprosarium. The orphanage included a general hospital and a home for the aged. The Saint was honored throughout Byzantine history as the patron of the orphanage.