Sardis in the Byzantine era is marked by a profound break. Before 616, it was the capital of a rich province, a large metropolis of a typical Roman and late antique type, adorned with imposing public buildings, providing extensive services for its large population, and a center of varied economic activities. Its destruction in the early seventh century is characterized by violent burning, extensively attested in the archaeological record, as the result of a Persian attack. The city was never rebuilt, and it declined to consist of a powerful hilltop fortification, with small settlements scattered over the ancient site, all built of or upon the ruins of the earlier city. 
In the time of Justinian, Sardis was the capital of the highly developed province of Lydia, which contained more than twenty cities and extensive agricultural and mineral resources. Earlier in the 4th century, Sardis had been the headquarters of an imperial weapons factory and had a philosophical school. The city was the center of a network of Roman roads that connected it with the Aegean and all parts of Asia Minor. Sardis was entered via a marble-paved east-west road lined with colonnades and shops, the “Byzantine Shops,” along the south wall of a grand bath and gymnasium complex, within which functioned the largest known synagogue in the Jewish diaspora. 
A Jewish community existed at Sardis among the pagans as early as the fifth century BC. It received considerable reinforcement in the Hellenistic era when around two thousand Jewish families to Lydia and Phrygia to pacify their rebellious inhabitants. Their greatest monument was the magnificent Synagogue built on the main street of the city, adjacent to the Gymnasium. The Synagogue was converted from the earlier building, which perhaps had been intended as an adjunct to the Gymnasium, and came to resemble a basilical church in plan. Surviving inscriptions show that the mosaic floors, the marble incrustations on the walls, and the paintings on the ceiling were contributed as offerings by pious members of the community. Most of the inscriptions found at the synagogue are written in Greek, the language in common use by the Jews of Asia Minor. 
The antiquity of the Christian community is attested in its listing among the seven churches of the province of Asia in the Book of Revelations. Yet there were still a significant number of pagans in Lydia and at Sardis in the time of Justinian. As civil organization was imitated by the Church, the bishop of Sardis became the metropolitan of the ecclesiastical province of Lydia, with the bishops of the other cities subject to him. The organization of the church proved more stable and more conservative than that of the state and it long outlived the system which had inspired it. As long as Christianity was predominant in the area, Sardis remained the metropolis of the province of Lydia. A three-aisled Christian basilica, “Church EA,” was built in the fourth century outside the city walls, which repaired and expanded through the seventh century. A large, unexcavated Justinianic basilica, “Church D,” stands in the center of the city. In addition, there was another church, “Church M,” located near the Temple of Artemis.
Construction of such a fortress (by far the largest of the region) illustrates the dominance of the military that marks the period and was notably manifested in the new administrative system, in which Sardis was no longer a capital but one of the bastions of the Thrakesion theme. It remained, however, the seat of the metropolitan archbishop, who retained his precedence in the church. Neither his headquarters nor the size of his establishment has been discovered. The fate of the Justinianic cathedral is unknown. It is possible that the bishop used Church EA in the western part of the city, which shows evidence of continuity through the whole period.
The only substantial church that provides evidence for this period is Church EA. It was rebuilt with solid walls and piers over the fallen colonnade in the nave and decorated with fresco in the ninth century, an indication that the church had some resources. By the eleventh century, however, its atrium and parts of the nave had become a cemetery, while the narthex was inhabited. Except for a partially occupied late antique villa adjacent to it, the church seems to have stood in an area that was largely deserted. 
The Laskarid period (1204–61) was a quite prosperous period for Sardis. At this time the old basilica (Church EA) was deliberately razed, and a new five-domed church (Church E) was built within its perimeter. Although it measures only 20 x 11 m, this was the first major construction in the city since the walls of the seventh century. It was built of brick and marble and was decorated with frescoes, gold and glass mosaics, and colored glass windows, perhaps made locally. Kilns for the production of brick, tiles, and pipe in the gymnasium could be associated with this construction. Yet this prosperity would not last very long. Threatened by the Turks in the late 13th century, its citadel was divided with them in 1304 and then Sardis definitively fell to Saruhan around 1315.