The Diocletianic or Great Persecution was the last and most severe persecution of Christians in the Roman Empire. In 303, the emperors Diocletian, Maximian, Galerius, and Constantius issued a series of edicts rescinding Christians' legal rights and demanding that they comply with traditional religious practices. Later edicts targeted the clergy and demanded universal sacrifice, ordering all inhabitants to sacrifice to the gods. The persecution varied in intensity across the empireweakest in Gaul and Britain, where only the first edict was applied, and strongest in the Eastern provinces. Persecutory laws were nullified by different emperors (Galerius with the Edict of Serdica in 311) at different times, but Constantine and Licinius' Edict of Milan (313) has traditionally marked the end of the persecution.

Christians had been subject to intermittent local discrimination in the empire, but emperors prior to Diocletian were reluctant to issue general laws against the religious group. In the 250s, under the reigns of Decius and Valerian, Roman subjects including Christians were compelled to sacrifice to Roman gods or face imprisonment and execution, but there is no evidence that these edicts were specifically intended to attack Christianity. After Gallienus's accession in 260, these laws went into abeyance. Diocletian's assumption of power in 284 did not mark an immediate reversal of imperial inattention to Christianity, but it did herald a gradual shift in official attitudes toward religious minorities. In the first fifteen years of his rule, Diocletian purged the army of Christians, condemned Manicheans to death, and surrounded himself with public opponents of Christianity. Diocletian's preference for activist government, combined with his self-image as a restorer of past Roman glory, foreboded the most pervasive persecution in Roman history. In the winter of 302, Galerius urged Diocletian to begin a general persecution of the Christians. Diocletian was wary, and asked the oracle of Apollo at Didyma for guidance. The oracle's reply was read as an endorsement of Galerius's position, and a general persecution was called on February 23, 303.

Persecutory policies varied in intensity across the empire. Whereas Galerius and Diocletian were avid persecutors, Constantius was unenthusiastic. Later persecutory edicts, including the calls for universal sacrifice, were not applied in his domain. His son, Constantine, on taking the imperial office in 306, restored Christians to full legal equality and returned property that had been confiscated during the persecution. In Italy in 306, the usurper Maxentius ousted Maximian's successor Severus, promising full religious toleration. Galerius ended the persecution in the East in 311, but it was resumed in Egypt, Palestine, and Asia Minor by his successor, Maximinus. Constantine and Licinius, Severus's successor, signed the Edict of Milan in 313, which offered a more comprehensive acceptance of Christianity than Galerius's edict had provided. Licinius ousted Maximinus in 313, bringing an end to persecution in the East.

The persecution failed to check the rise of the Church. By 324, Constantine was sole ruler of the empire, and Christianity had become his favored religion. Although the persecution resulted in death, torture, imprisonment, or dislocation for many Christians, the majority of the empire's Christians avoided punishment. The persecution did, however, cause many churches to split between those who had complied with imperial authority (the traditores), and those who had remained "pure". Certain schisms, like those of the Donatists in North Africa and the Melitians in Egypt, persisted long after the persecutions. The Donatists would not be reconciled to the Church until after 411. Some historians consider that, in the centuries that followed the persecutory era, Christians created a "cult of the martyrs", and exaggerated the barbarity of the persecutions. Other historians using texts and archeological evidence from the period assert that this position is in error. Christian accounts were criticized during the Enlightenment and afterwards, most notably by Edward Gibbon. This can be attributed to the political anticlerical, and secular tenor of that period. Modern historians, such as G. E. M. de Ste. Croix, have attempted to determine whether Christian sources exaggerated the scope of the Diocletianic persecution, but disagreements continue.

The Roman emperor was the ruler of the Roman Empire during the imperial period (starting with the granting of the title augustus to Octavian in 27 BC). The emperors used a variety of different titles throughout history. Often when a given Roman is described as becoming "emperor" in English it reflects his taking of the title augustus (and later basileus). Another title often used was caesar, used for heirs-apparent, and imperator, originally a military honorific. Early emperors also used the title princeps civitatis ('first citizen'). Emperors frequently amassed republican titles, notably princeps senatus, consul, and pontifex maximus.

The legitimacy of an emperor's rule depended on his control of the army and recognition by the Senate; an emperor would normally be proclaimed by his troops, or invested with imperial titles by the Senate, or both. The first emperors reigned alone; later emperors would sometimes rule with co-emperors and divide administration of the empire between them.

The Romans considered the office of emperor to be distinct from that of a king. The first emperor, Augustus, resolutely refused recognition as a monarch. For the first three hundred years of Roman emperors, from Augustus until Diocletian, efforts were made to portray the emperors as leaders of the republic, fearing any association with the kings of Rome prior to the Republic.

From Diocletian, whose tetrarchic reforms also divided the position into one emperor in the West and one in the East, until the end of the Empire, emperors ruled in an openly monarchic style and did not preserve the nominal principle of a republic, but the contrast with "kings" was maintained: although the imperial succession was generally hereditary, it was only hereditary if there was a suitable candidate acceptable to the army and the bureaucracy, so the principle of automatic inheritance was not adopted. Elements of the republican institutional framework (senate, consuls, and magistrates) were preserved even after the end of the Western Empire.

The reign of Constantine the Great witnessed the removal of the Caput Mundi from Rome to Constantinople, formerly known as Byzantium, in 330 AD. The Western Roman Empire collapsed in the late 5th century after multiple invasions of imperial territory by Germanic barbarian tribes. Romulus Augustulus is often considered to have been the last emperor of the West, until his forced abdication in 476, although Julius Nepos maintained a claim recognized by the Eastern Empire to the title until his death in 480. Following Nepos' death, the Eastern emperor Zeno abolished the division of the position and proclaimed himself as the sole emperor of a reunited Roman Empire. The subsequent Eastern emperors ruling from Constantinople continued to style themselves "Emperor of the Romans" (later βασιλεύς Ῥωμαίων in Greek), but are often referred to in modern scholarship as Byzantine emperors. Constantine XI Palaiologos was the last Roman emperor in Constantinople, dying during the Fall of Constantinople to the Ottoman Empire in 1453.

The "Byzantine" emperors from Heraclius in 629 and onwards adopted the monarchic title of basileus (βασιλεύς), which became a title reserved solely for the Roman emperor and the ruler of the Sasanian Empire. Other rulers were then referred to as rēgas.In addition to their pontifical office, some emperors were given divine status after death. With the eventual hegemony of Christianity, the emperor came to be seen as God's chosen ruler, as well as a special protector and leader of the Christian Church on Earth, although in practice an emperor's authority on Church matters was subject to challenge.

Due to the cultural rupture of the Turkish conquest, most western historians treat Constantine XI as the last meaningful claimant to the title Roman emperor. From 1453, one of the titles used by the Ottoman Sultans was "Caesar of Rome" (Turkish: Kayser-i Rum), part of their titles until the Ottoman Empire ended in 1922. A Byzantine group of claimant Roman emperors existed in the Empire of Trebizond until its conquest by the Ottomans in 1461, though they had used a modified title since 1282.

Eastern emperors in Constantinople had been recognized and accepted as Roman emperors both in the East, which they ruled, and by the papacy and Germanic kingdoms of the West until the deposition of Constantine VI and accession of Irene of Athens as Empress regnant in 797. Objecting to a woman ruling the Roman Empire in her own right and issues with the eastern clergy, the Papacy would then create a rival lineage of Roman emperors in western Europe, the Holy Roman Emperors, which ruled the Holy Roman Empire for most of the period between 800 and 1806. These emperors were never recognized as Roman emperors by the court in Constantinople and their coronations resulted in the medieval problem of two emperors.