For two centuries after the destruction of the city by the Herulians, Athens faced many challenges and destruction, yet the city gradually recovered and experienced a new period of prosperity. This was largely due to the continued existence of the philosophical schools that were attended by men from all over the Mediterranean. However, these schools were strongholds of religious beliefs that were going out of style, and strong reactions from the Byzantine emperors were not long in coming.

In 529 CE, the emperor Justinian banned the teaching of philosophy and the operation of the schools of Athens, ending a tradition of more than one thousand years. But the decisive blow came from an invasion by the Slavs in 582/3 CE. The city was once more reduced to ruins.

From the middle of the 5th century CE, most of the ancient Greek temples of Athens were converted into churches and many new Christian churches were constructed. The Parthenon was converted into a Christian church, first dedicated to Virgin Mary and then to Panagia Atheniotissa (Church of Our Lady of Athens). Shortly before the middle of the 8th century CE, the city was ecclesiastically promoted to become a Metropolis and began to show remarkable growth.

A large number of churches were built in Athens from the 10th to the 12th century, and the total number of Athenian churches has been estimated to have reached forty. Some are preserved in their original form or with some minor interventions, among them the Church of Agioi Asomatoi in Thissio and the Kapnikarea on Ermou Street.

In the last quarter of the 12th century, Athens experienced another great disaster from the invasion of the Saracens who occupied the city and left it in ruins. Its inhabitants were plagued by disease and hunger. The city was easy prey for the Franks who conquered it in 1204 and established the Duchy of Athens.

Two and a half centuries of Latin rule (Franks, Catalans and Florentines) followed in which Athens went into decline. The monuments of the city were hardly left unscathed. The western side of the Acropolis and the Propylaia was fortified with bastions and turned into a tower with Frankish design and was later made into a command post and a palace for the Duchy of Athens. The Erechtheion became the residence of the Catholic Bishop, and the Parthenon became a Catholic Cathedral.