The best known and most celebrated shrine of the Holy Virgin in Constantinople was the church of Panagia of Blachernae. The history of the shrine, the fame of which had spread throughout the Christian world, extends over the entire Byzantine era, and the great events associated with it are linked with the history of the City.The first church at the site of the sacred spring was built and decorated by the Augusta Pulcheria between 450-453 (the year of her death) and her husband, the Emperor Marcian (450-457). The church was completed and embellished further by the Emperor Leo I (457-474), who added theHagiasma (fountain of holy water) and the Hagion Lousma (sacred bath). Leo I also built the parecclesion of the Hagia Soros to house the holy mantle and robe of the Virgin that had been brought from Palestine to Constantinople in 473. It was then that the church was endowed with large estates. Procopius writes that Justinian, during the reign of his uncle Justin I (518-527) had altered and improved the original building. Procopius's description suggests that the basilica was given a dome supported by columns forming a semicircle. This renovation is mentioned in two epigrams of the Palatine Anthology.

At times, Emperors showed their personal interest for the church by making donations and adding new constructions and decorations. Justin 11 (565-578) added two apses remodelling the plan into a trefoil transept, and some centuries later Romanus III Argyrus (1028-1034) decorated with gold and silver the intrados of the arches. A measure of the importance of the shrine is found in Emperor Heraclius's Neara, which appoints a total of 74 persons to the service of the church: 12 presbyters, 18 deacons, 6 deaconesses, 8 sub deacons, 20 readers, 4 chanters and 6 door keepers .

The role played by the Panagia of Blachernae during the Iconoclast crisis, particularly in the reign of Constantine V, should be stressed. Like the Hagia Sophia, this church was a center of Orthodox worship where every Friday an all-night vigil was dedicated to the miracle-working icon of the Virgin. Because of this, the whole iconographic program of the church was destroyed by the iconoclasts. In the Life of St. Stephenthe Younger, a contemporary work written in 808, it is recorded that the iconoclasts replaced the images of Christ, the Virgin and Saints with representations of trees, birds and animals: "Having ruined the venerated church of the Immaculate Theotokos of Blachernae, the walls. of which had been painted with varied iconographic subjects from God's Incarnation and His many Miracles to His Ascension and the Descent of the Holy Spirit, thus exalting Christ's mysteries, they turned it into a place of fruit-storing and omnithoscopy. They decorated it, to tell the truth indecorously, with all kinds of trees and birds and wild beasts and other animals within roundels of ivy-leaves, and cranes and crows and peacocks".

The disappearance of the historic icon of the Virgin, painted on wood and revetted with gold and silver, is dated to those years. According to tradition, the icon was discovered hidden behind a w all in 1030, when the Emperor Romanus III Argyrus was renovating the church.

From the surviving sources we learn that the church of Blachernae was located near the shore of the Golden Horn, outside the city walls. To protect it, Emperor Heraclius built a defence wall around the shrine. Later, when the Palace of Blachernae was erected further up on the slope of the hill, a special gate and stairway connected the church with the Palace. Emperors often attended services at the Panagia of Blachernae and showed their interest and respect for the shrine in many ways. Campaigning Emperors are known to have carried an icon of the Panagia of Blachernae and a great number of imperial seals bear the image of the Blachernitissa.

The litany celebrated every Friday at the church of St.Mary in the Chalkopratiae with the icon of the Virgin Blachernitissa had been established since the time of the Patriarch Timotheus I (511 -518) . Some other feast-days were commemorated with special pomp at the church of Blachernae: The Presentation of Christ in the Temple (2nd February), the Feast of Orthodoxy (First Sunday of Lent), Good Friday, Easter Tuesday, the ceremony for the Virgin's Veil (2nd July), the consecration of the church (3Ist July), the saving of the City from the Avars and the Persians (7th August), the Dormition of the Virgin (15th August) and the event of the terrible earthquake of 740 (26th October).

The shrine of Blachernae, "the great church" as it is called in written sources, was composed of three buildings: the main church, the parecclesion of the Hagia Soros and the Hagion Lousma.