Among Libyan cities, Derna has a unique location and physical environment, as it lies between the Jebel Akhdar (also known as Green Mountain), the Mediterranean Sea, and the desert and is the fourth most important port in Cyrenaica's northern coast after Benghazi, Bayda and Tobruk.

The city was the location of the famous Battle of Derna (1805), the first victory achieved by the United States Military on foreign soil.

In addition, John Moschus speaks of a bishop Thedodorus of Darnis as having had a vision of Saint Leo the Great in the mid-5th century.

[15] The city was resettled by the refugees from Islamic Spain (Expulsion of the Moriscos) 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 1835, when it became a dependency of the autonomous sanjak of Benghazi, essentially Cyrenaica, which was governed directly from Constantinople.

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.

Lieutenant and former Consul to Tripoli William Eaton—who had marched 500 miles (800 km) across the Libyan Desert from Alexandria—captured the city as part of the First Barbary War.

The Italian rule over Derna lasted 29 years, 3 months, and 14 days until it was captured on 30 January 1941 by Australian Troops during the Second World War's North African Campaign.

[22] Following mass protests on 18 February 2011, the city came under the control of the National Transitional Council, breaking from the Libyan government.

[25] In November 2014, al-Baghdadi released an audio-recording accepting the pledge of allegiance and announced the expansion of his group.

However, Derna is near the fertile upland area of eastern Libya, which is the wettest region in the country, receiving some 600 millimetres (24 in) of precipitation annually.

[39] The Abu Mansur and Derna dams upstream of the city were meant to control soil erosion and prevent flooding.

Derna features a hot semi-arid climate (Köppen BSh) with strong Mediterranean influences: essentially all the modest annual rains fall between October and March.