Damascus is known to be the oldest continuously inhabited city in the world. There is firm evidence that in the third millennium BC, Damascus was a population center of a civilization that was considerably prosperous and economically influential. The earliest reference to the city was found in the archaeological site of Ebla in 1975; where the word "Damaski" was found on one of the clay tablets. Some historians believe that the city actually dates back to the seventh millennium BC.

Damascus remained much the same as it had during the Roman period, except for the mass construction of churches and the transformation of the Temple of Jupiter into a cathedral dedicated to St. John the Baptist in the fourth century. In addition to this cathedral, 16 churches were built in and around Damascus. The Church of al-Mosallaba was built near the Eastern Gate at the site where the Chapel of Ananias now stands. The site has been chosen because it's thought to be the place where St. Paul was cured of his blindness after his vision on the road to Damascus. Two churches were also built in this area: The Church of al-Maqsala'at and the Church of Mariam (Mary), which was replaced by the Maryamiyyah Church which still stands there today. There are descriptions of other churches, but no remains of which were found.