She was born in Rome and reared in the love of Christ. She secretly left her parents' house and traveled by ship to Alexandria, where she found lodging with four virtuous pagan maidens. By her example and counsel these four were in time led to abandon idolatry and embrace Domnica's faith. The five then sailed to Constantinople, where it is said that the Patriarch Nectarius (October 11) was notified of their coming by an angel and met them at the dock. The Patriarch baptized the four maidens himself, giving them the names Dorothea, Evanthia, Nonna and Timothea, then settled them and Domnica in a monastery.

Soon the fame of Domnica's pure life, wise teaching, and wondrous healings spread throughout the city, and even the Emperor Theodosius, with the Empress and his court, came to see her. Soon the crowds made it impossible for her and her sisters to live the heavenly life for which they had entered the monastery; so they relocated the monastery to a remote, demon-haunted location where executions had once commonly been performed, since everyone avoided the area. Here a new monastery was built by order of the Emperor, and the sisters found peace.

Saint Domnica's fame continued, and she became not only a healer but an oracle for the city of Constantinople, prophesying the death of the Emperor Theodosius and the unrest which followed it. She reposed in peace, having first entrusted the care of the monastery to Dorothea. At the moment of her death, the whole monastery was shaken, and those present saw Saint Domnica dressed as a bride, being borne heavenward escorted by a company of white-clad monks and nuns.