He was a native of Thessalonica, born of noble parents. His wisdom and distinction in battle earned him rapid advancement in the service of the Empire: in time he was appointed commander of all the Roman forces in Thessaly, and Proconsul of Hellas. Despite these worldly honors, Demetrius put his Christian faith before all, and by his words and example brought many pagans to faith in Christ.

When the Emperor Maximian, a persecutor of Christians, came to Thessalonica he appointed games and public sacrifices to celebrate his recent victory over the Scythians. Some jealous pagans used the visit to denounce Demetrius to the Emperor. Maximian had Demetrius cast into a fetid cell in the basement of some nearby baths. Maximian had brought with him a huge barbarian of tremendous strength named Lyaios, who fought many men in the arena and defeated them all, to the entertainment of the Emperor and the crowds. A young Christian named Nestor determined to show the people that the only true strength is in Christ: he visited Demetrius in his cell and asked for his blessing to challenge Lyaios to combat. The Martyr made the sign of the Cross over Nestor and sent him to the arena with his blessing. Nestor, a young boy, cried out before the Emperor 'God of Demetrius, help me!' and quickly killed the mighty Lyaios, to the astonishment of the crowd. The infuriated Emperor had Nestor slain with his own sword, and sent soldiers to Demetrius' cell, where they killed him with their spears. Demetrius' servant, a believer named Lupus, retrieved the body of Demetrius and buried it with honor. He kept the Saint's ring and blood-stained tunic, and through them worked several miracles and healings. When the Emperor heard of this, he had Lupus, too, beheaded.

As a sign of the grace that rested on the holy Demetrius, a fragrant myrrh flowed copiously from the Martyr's body after his death, healing many of the sick. For many centuries, St Demetrius has been a patron Saint of Thessalonica.