Born near Kiev, he was raised in piety and, at the early age of eleven, entered the Ecclesiastical Academy of Kiev. At the age of seventeen he was professed as a monk. A few years later he was ordained to the priesthood. Despite his constant desire to retire into a life of asceticism and solitude, his many gifts were needed by the Church and, much against his will, he spent most of his life engaged in writing and other labors. The Abbot of the Lavra of the Kiev Caves, knowing his scholarly abilities, called him to compile a Russian-language Lives of the Saints, a work to which he devoted himself tirelessly for twenty-five years.

This compilation was not a dry exercise for him; he approached each Saint's life with prayer, and was often granted visions. The holy Martyr Barbara appeared to him in his sleep in 1685; when he asked her to intercede for him to the Lord, she chided him for praying "in the Latin Way," that is, for using short prayers. Seeing his distress at being so rebuked, she smiled and said "Do not be afraid!"

St Demetrius was elevated to the episcopal throne (of Metropolitan of Tobolsk and Siberia) in 1701, but asked to be transferred due to ill health, and because the Siberian see would not allow him to continue his research. So he was appointed to the Diocese of Rostov in 1702; he received a divine revelation that he would end his years there. He completed his monumental Lives of the Saints in 1705; thereafter he devoted his energies to the care of his flock, the education of priests, and many spiritual writings, including several addressed to the schismatic "Old Believers," pleading with them to rejoin the canonical Church.

Despite his poor health, he maintained a life of strict prayer and fasting, and encouraged his faithful, in his sermons and writings, to do the same. He predicted his own death three days beforehand. The Synaxarion concludes: "the holy Bishop fell at the feet of his servants and chanters, and asked their forgiveness. Then, with an ardent prayer on his lips, he shut himself in his cell. The next morning, 28 October 1709, they discovered him dead upon his knees. The relics of Saint Demetrius were found incorrupt in 1752 and they wrought many healings. He was formally glorified by the Church in 1757."