On 27 December, 537 the new Hagia Sophia was inaugurated by the patriarch Menas. It replaced an earlier cathedral built under Constantius II (337-61) and dedicated in 360. Preceded by a forecourt or atrium, the church of Constantius II was a wooden-roofed basilica with a nave flanked by two or perhaps four side aisles, each carrying a gallery storey, perhaps much like the Constantinian basilica of the Holy Sepulchre at Jerusalem. Later Byzantine sources mention marble columns in the fourth-century cathedral.

A baptistery known as `Olympas' stood inside or probably adjacent to the church, and an episcopal palace of at least two storeys was to its south side, from whence John Chrysostom is said to have `come down to the church' to pray. The first cathedral was known as the Great Church - the name Hagia Sophia, referring to Christ as the Wisdom (Sophia) of God, not being attested until c. 430. The cathedral of Constantius burned in the year 404. There is no report on how extensive the damage was, but as the building was functioning again by 406, repairs must have been limited. More work was done under Theodosius II (408-50) and the church was rededicated in 415. Whether the original fourth-century planning was changed at this juncture remains undocumented. Remnants of the fourth and early fifth-century churches are visible today in front of the entrance of the present church and in its courtyard. They consist of the flight of six steps leading up to the stylobate of a monumental portico and, about 4 m (13 ft) eastward, the stretch of an early wall. A number of architectural blocks belonging to the portico were excavated by Alfons Maria Schneider in 1935, who demonstrated that the centre of the entrance portico projected from the monumental colonnade and featured a pedimental porch with an arcuated lintel. As Schneider showed, the style of the sculptural ornament of these blocks discloses that they were carved in the time of Theodosius II.

The stretch of the early wall to the east of this portico is most probably the eastern wall of the atrium rather than the church itself. It is constructed of alternate bands of brickwork and of mortared rubble work, faced with courses of small, very roughly square stone (currently capped by several courses of modern masonry). The pre-Justinianic church was smaller than its sixth-century replacement, seems to have been aligned at an angle of about a couple of degrees further toward the south, and consisted of elements that were standard features of Constantinopolitan church planning in the early Byzantine period: an atrium, perhaps a narthex, and an aisled basilica with galleries.

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