很多人認為君士坦丁一世(公元306-337年在位)是第一個“拜占庭皇帝”。是他於公元324年把帝國首都從尼剋美狄亞遷到拜占庭，並把後者重建為君士坦丁堡，也稱Nova Roma(“新羅馬”)。羅馬城本身從戴剋裏先治下開始就不再作為帝國首都。有人把帝國的起源追溯到狄奧多西一世統治時（379年-395年）和基督教正式取代羅馬異教，或者從他395年去世時東西方政治永久性分裂算起。其他人將其定為之後的476年，傳統上認為的最後一個西羅馬皇帝羅慕路斯·奧古斯都被廢黜時，衹剩下東方希臘化地區的皇帝作為帝國的唯一權威。也有人認為是希拉剋略在位時（約620年）的帝國改組，拉丁文的頭銜和使用被正式改為希臘文。無論如何，這種轉變是逐漸的，至330年君士坦丁在他的新首都舉行落成典禮時，希臘化和不斷深入的基督教化已經開始。一般認為帝國於君士坦丁堡1453年陷落於鄂圖曼土耳其帝國後滅亡。
公元541-541年，全國流行的查士丁尼大瘟疫折磨着拜占庭帝國，包括它的首都君士坦丁堡。據估計查士丁尼大瘟疫使全世界1億人喪生。它使541年至700年間的歐洲人口減少約50%，可能也是阿拉伯人徵服成功的原因之一。
Many consider Emperor Constantine I (reigned 306–337) to be the first "Byzantine Emperor". It was he who moved the imperial capital in 324 from Nicomedia to Byzantium, refounded as Constantinople, or Nova Roma ("New Rome"). The city of Rome itself had not served as the capital since the reign of Diocletian. Some date the beginnings of the Empire to the reign of Theodosius I (379–395) and Christianity's official supplanting of the pagan Roman religion, or following his death in 395, when the political division between East and West became permanent. Others place it yet later in 476, when Romulus Augustulus, traditionally considered the last western Emperor, was deposed, thus leaving sole imperial authority with the emperor in the Greek East. Others point to the reorganization of the empire in the time of Heraclius (ca. 620) when Latin titles and usages were officially replaced with Greek versions. In any case, the changeover was gradual and by 330, when Constantine inaugurated his new capital, the process of hellenization and increasing Christianization was already under way. The Empire is generally considered to have ended after the fall of Constantinople to the Ottoman Turks in 1453. The Plague of Justinian was a pandemic that afflicted the Byzantine Empire, including its capital Constantinople, in the years 541–542. It is estimated that the Plague of Justinian killed as many as 100 million people across the world. It caused Europe's population to drop by around 50% between 541 and 700. It also may have contributed to the success of the Arab conquests.