A combination of internal turmoil and the threat of invasion by various nomadic tribes to the north and east led to a crisis in the third century. The Germanic Heruli sacked Athens in A.D. 267. The Goths, the Alemanni, the Franks, and the Vandals all made significant incursions into the empire. In the east, the Sassanians revived the moribund Persian Empire and defeated Roman armies several times during the third century.

The chaos of the third century raised deep social and economic problems throughout the empire. Taxes increased to expand the army, driving the peasantry further into poverty. The economy nearly collapsed as the coinage was devalued to provide the vast amounts of metal needed to pay the army. Inflation was rampant. Manpower was scarce because of huge military losses, plagues, and the weakened condition of the peasantry. Such traumas set the Latin West and the Greek East onto separate historical trajectories. The urban centers of the East, built upon the structure of the old Greek polis, endured the crises much better than the other areas of the empire.

The reigns of Diocletian and Constantine mark a critical turning point in the fortunes of the empire. Constantine became emperor of Rome in A.D. 305. He built on the foundations laid by his predecessor, Diocletian, and consolidated the empire after a chaotic third century in which the average reign of a Roman emperor was less than five years. The reforms that Diocletian and Constantine introduced brought temporary stability. Diocletian responded to geographic fragmentation by dividing the empire into two major parts to be ruled by separate emperors. Constantine's Edict of Milan, issued in 313, established the empire's toleration of Christianity; his personal conversion continued over a number of years.

In 330 Constantine advanced the separation of the eastern and western empires by establishing his capital at Byzantium and renaming it Constantinople. In 364 the empire was officially split. The western empire was to be ruled from Rome, the eastern from Constantinople. For those in the eastern territory that had been dominated by the tradition of the polis, the transition from a Latin Roman empire to a Greek Byzantine empire was an easy one. Constantinople inherited the cultural wealth of the Greek citystate as a solid foundation and a symbol of civilization in its empire.