In the Hellenistic period the ancient city was part of the Libyan Pentapolis. Under Rome, it became a civil and later the religious metropolis of Libya Secunda, or Libya Inferior, that is the Marmarica region.
It was a metropolitan titular archbishopric in the former Roman province of Libya, in the diocese of Egypt. However, only three, perhaps four, bishops are known, from the fourth or sixth century to about 600.
The city was resettled by the Islamic refugees from Spain (Al-Andalus) in 1493 on the site of the ancient settlement.
Under Ottoman rule, Derna was initially under the governor at Tripoli, but shortly after 1711 it fell under the Karamanli sultanate, until in 1835 when it became a dependency of the autonomous sanjak of Benghazi, essentially Cyrenaica, which was governed directly from Constantinople. which in turn, in 1875, became the vilayet of Cyrenaica. In the 1850s it had an estimated 4,500 inhabitants, who lived by agriculture, fishing and the coastal trade.
The oldest mosque in Derna is Al-masjeed al-ateeq, or the "Old Mosque", restored by wali Mahmoud Karamanli in 1772, vaulted with 42 small cupolas. This kind of vault was in use due to lack of some materials, like timber or stone in the region of Cyrenaica. There is another mosque, named Masjeed az-zawiyah, built in 1846, more strictly curved in side of a hill.
The French admiral Gantheaume landed at Derna in June 1800 in an attempt to reinforce Napoleon in Egypt by bringing troops overland, but was rebuffed by the local garrison.
Derna was the location of the 1805 Battle of Derne, in which forces under U.S. General William Eaton�who had marched 800 kilometres (500 mi) across the Libyan Desert from Alexandria�captured the city as part of the First Barbary War.
On 30 January 1941, Australian troops captured Derna from the Italians in the North African Campaign. On 6 April 1941, Germans retake Derna from the British. On 15 November 1942, British
