Pinpointing when the Parthenon stopped being a temple is harder than it sounds. The decree of Theodosius II in 438 ordered the conversion of pagan temples across the empire. The edict of Justinian in 529 closed the classical schools of philosophy. Between those two dates, the Athenian polytheist tradition fell quiet. The last recorded dedication inside the Parthenon by a polytheist worshipper is dated to 375. The last Panathenaic Games, the great procession that had wound up the Acropolis to honor Athena for nearly a thousand years, were held in either 391 or 395. F.W. Deichmann's archaeological work has shown that conversion to a church must have occurred before 578 to 582, based on Christian tombs with datable coins found on the south side of the building. Somewhere in those two centuries, between Theodosius and Deichmann's tombs, Athena left and Mary moved in.

The architects of the conversion did not start with a clean canvas. They started with a temple that had survived a major fire, lost its outer roof, and was now a half-shell of marble columns standing open to the weather. Only the naos, the inner chamber where Athena's huge gold-and-ivory statue had once stood, was reroofed. The peripteral colonnade, the famous outer ring of columns, was left exposed. From this strange half-temple they built a basilica. The naos became the nave. The opisthodomos, the back porch, became the narthex, with a screened-off baptistry. The walls between intercolumnar spaces of the pronaos were filled in to create a single doorway facing west. New doors were cut on the north and south. The pronaos at the eastern end was walled off and rounded into a semicircular apse. Where Phidias' statue of Athena had stood, an altar to Mary now sat.

The conversion changed the building. It also marked it. Modern scholars have catalogued some 232 pieces of graffiti scratched into the Parthenon's marble during the Christian period. Sixty of them are dated. Together they form one of the most extraordinary records anywhere of how ordinary worshippers used a working church. Names. Prayers. Crosses. The deaths of priests and the visits of pilgrims. Where stone usually keeps its secrets, the Athens basilica was marked up by the people who attended it. Less benignly, the conversion involved deliberate vandalism of classical sculpture. Parts of the famous Parthenon frieze were cut away to make clerestory windows above the new nave. The metopes, the carved square panels of the original Doric frieze, were systematically defaced, with most of the figures hammered or chiseled. A few were spared. The German scholar Rodenwalt argued that those spared were given an interpretatio christiana, a Christian reinterpretation, that allowed them to remain. Later scholarship has questioned whether the choice was that systematic. When the defacement happened, and who did it, remains unresolved.

After the Fourth Crusade sacked Constantinople in 1204, Athens fell to a Frankish lord. The Pope made the church a Catholic archiepiscopal cathedral by Papal Bull in 1206, and Our Lady of Athens spent the next two and a half centuries hosting the Latin liturgy instead of the Greek. The church became a center of Crusader Athens, attended by knights and ladies of the small French-speaking court that ruled the city. Power changed hands several times. Catalan mercenaries took over in 1311. Florentines took over in 1388, and in 1458, when the last Florentine Duke of Athens was finally driven out, the Parthenon briefly returned to the Orthodox faith of the Greek population. The reversion did not last long. Sometime after the Ottoman conquest in 1460, the building was converted again, this time into a mosque. A minaret was added at the southwest corner. The rest of its pre-1687 history would unfold under Islamic worship, until a Venetian shell on September 26, 1687 hit the gunpowder stored inside and blew the roof off the building forever.