The city was founded before the fourteenth century and gradually became the most important Tuareg city, supplanting Assodé, by growing around trans-Saharan trade. The city still sees the arrival of caravans, bringing salt from Bilma.

In 1449, Agadez became a sultanate, while around 1500 it was conquered by the Songhai Empire. At this point, the city had a population of around 30,000 people and was a key passage for the medieval caravans trading between the West African cities of Kano and Timbuktu and the North African oases of Ghat, Ghadames, and Tripoli, on the Mediterranean shore. Decline set in after the Moroccan invasion, and the population sank to less than 10,000.