The region of Djanet has been inhabited since Neolithic times. There were periods of ten thousand years at a time that the area was not desert. The flora and fauna were luxuriant as is seen in the numerous rock paintings of Tassili n'Ajjer around Djanet. Populations of hunter-gatherers lived there.

Djanet was founded in the Middle Ages by the Tuareg. The Ottoman Empire, which had a nominal authority over the Fezzan region, reinforced their presence in the area at the beginning of the 20th century in reaction to the colonization of Africa by the Europeans.