In the 1st and 2nd century Athens was a wealthy city and one of the empire’s major intellectual centres, which frequently attracted the attention and patronage of emperors and wealthy civilians. Hadrian increased the perimeter of the walls and almost doubled the city’s area. Herod Atticus adorned it with groups of monuments that have survived in part to this day. That being said, serious damage was done when the one-time glorious city was taken by the Heruli in 267, and raided by the Goths under Alaric in 396. The Acropolis, the Roman agora and Hadrian’s Library were surrounded by a wall, which became Athens’ main fortification. Plato’s Academy was revitalized from the early 4^th to the early 6^th century by the neo-platonic philosophers, who taught rhetoric and philosophy to promising Christian and pagan youths from all over the empire; three of its students were Basil the Great, Gregory of Nazianzus and Emperor Julian . Empress Pulcheria was so impressed by the education received by Athinaïs, daughter of the sophist Leontius, that in 421 she had her forcibly christened Eudocia and wed her to her brother, Emperor Theodosius II. The so-called Palace of Giants, founded in the ancient agora in this period, may have belonged to Eudocia and her family.
 
Christianity began to make its presence felt in the city in the early 5^th century. A tetraconch which may from the outset have been a Christian church was erected inside Hadrian’s Library, in addition to a three-nave basilica on the island in the middle of the Ilissos River, which may have been dedicated to the memory of Leonides, bishop of the city.

Shortly before the middle of the same century, the Parthenon was converted into the city’s cathedral church and dedicated to the Virgin Mary. The inhabitants who remained faithful to the idols seem to have lived in fear. Although the Panathenaic procession continued to be celebrated up until the 5th century, offering a sense of respite, it was stripped of pagan rituals. In 529 the Academy and the remaining schools were closed by decree of Justinian , though whether this was ever enforced remains a subject of debate. This sealed the economic decline of a city that had once and for all lost its role as a centre of learning. The opulent residences unearthed in the vicinity of the Areios Pagos were abandoned by their occupants, either because they were unable to maintain them in times of recession or because the Slavs appeared in the late 6^th century.
 
In the following centuries written sources mentioning Athens are sporadic. Emperor Constans II, his army and court wintered in Athens in 662-663 while preparing a campaign against Sicily. Relations between the local nobility and the palace of Constantinople probably began at this time. Two Athenian women became empresses: Irene, who was on the throne from 780 to 802; and her niece Theophano, who ruled for a few months in 811. In the early 9th century the city was promoted from a diocese to an archdiocese, in accordance with the palace’s wishes rather than on account of any increase in the population. Private houses were located in neighbourhoods to the north, west and south-west of the Acropolis, within and beyond the Late Roman wall. They were generally of makeshift construction, with rooms arranged around a courtyard, next to workshops and small factories. Excavations have mainly brought to light house basements full of storage jars. From the late 10^th century, small churches were built in the area north of the Acropolis. These had clearly defined outlines and were strongly built of cloisonné masonry , with domes surrounded by small marble columns. Such churches include Agioi Theodoroi in Klafthmonos Square (1049); the oldest surviving church is most probably the catholicon in Asomatoi Monastery (dedicated to the Incorporeal Saints), better known as Petraki Monastery, from the late 10^th century. Agios Eleftherios (the Small Metropolis or cathedral) can be placed in the late 12th century. It is not known whether these churches were privately owned or served as the catholica of small monasteries. Basil II the Bulgar Slayer arrived in 1018 to pray in the Church of the Virgin Mary at Athens, as the Parthenon was then called. His visit ushered in a period of growth for the city cathedral as a pilgrim shrine. However, letters written by the scholar Metropolitan Nicetas Choniates in the late 12th century express sadness at the poverty and illiteracy of the people, the destruction of houses, the poor state of the walls, the greed of government officials and pirate raids.

In 1204 Choniates held out against Leo Sgouros by gathering the population in the Acropolis. Shortly afterwards he was forced to surrender the city to Boniface of Montferrat, who appointed Guy de la Roche as its first Great Lord; in 1259 the city formed part of the Duchy of Athens, which stretched from Lokris to the Corinthian Gulf and from Evia to Doris. The de la Roche Burgundians erected the Rizokastro, a new wall around the Acropolis incorporating a large part of the Late Roman one. This period­­­­ of adjustment under the rule of the de la Roches, including the appointment of a Latin bishop in the cathedral in 1204, favoured the founding or renovation of new churches in outlying areas only; in the late 13^th century additions were made to the wall paintings in the so-called Omorphe Ecclesia (“Beautiful Church) in Galatsi. Daphni Monastery was ceded to Cistercian monks and its catholicon became the burial place of the Dukes of Athens.

From 1311 to 1388 the city passed into the hands of the Catalan Company, which was notorious for the cruelty of its administration, while in 1385 the Catalans gave it to Nerio Acciaioli, scion of the renowned Florentine family that held the sovereignty of Athens until 1456, apart from a brief period from 1394 to 1403 when it was under the control of the Venetians. Under the Acciaioli the capital of the duchy was transferred from Thebes to Athens, the palace at the Propylaea and the Parthenon were renovated, roads were built and a tall tower was erected at the entrance to the Acropolis fortifications. In 1456 the last Florentine duke handed Athens over to the Turks. Two years later this led Mehmed the Conqueror to grant the Athenians privileges, including the right to retain all churches except for the Parthenon, which was converted into a mosque.