Approximately 100 years after the destruction of Punic Carthage in 146 BC, a new city of the same name was built on the same land by the Romans in the period from 49 to 44 BC. By the 3rd century, Carthage had developed into one of the largest cities of the Roman Empire, with a population of several hundred thousand. It was the center of the Roman province of Africa, which was a major breadbasket of the empire. Carthage briefly became the capital of a usurper, Domitius Alexander, in 308–311. Conquered by the Vandals in 439, Carthage served as the capital of the Vandal Kingdom for a century. Re-conquered by the Eastern Roman Empire in 533–534, it continued to serve as an Eastern Roman regional center, as the seat of the praetorian prefecture of Africa. The city was sacked and destroyed by Umayyad Arab forces after the Battle of Carthage in 698 to prevent it from being reconquered by the Byzantine Empire. A fortress on the site was garrisoned by Muslim forces until the Hafsid period, when it was captured by Crusaders during the Eighth Crusade. After the withdrawal of the Crusaders, the Hafsids decided to destroy the fortress to prevent any future use by a hostile power. Roman Carthage was used as a source of building materials for Kairouan and Tunis in the 8th century.

Byzantine rule in North Africa spanned around 175 years. It began in the years 533/534 with the reconquest of territory formerly belonging to the Western Roman Empire by the Eastern Roman (Byzantine) Empire under Justinian I and ended during the reign of Justinian II with the conquest of Carthage (698) and the last Byzantine outposts, especially Septem (708/711), in the course of Islamic expansion.