Agadez was founded before the 14th century, and, by growing around trans-Saharan trade, gradually became the most important city of the Tuareg people, supplanting Assodé. The city still sees the arrival of caravans bringing salt from Bilma.

In 1449 Agadez became a sultanate, but was later conquered by the Songhai Empire in 1515,[1] remaining a part of that empire until 1591.[2] At this point, the city had a population of around 30,000 people By then, the city was a key passage for the medieval caravans trading between the West African cities of Kano (the source of the Hausa language which is the traditional lingua franca between different ethnic groups in the city, especially in the area of trade, religion and administration) and Timbuktu, and the North African oases of Ghat, Ghadames, and Tripoli, on the Mediterranean shore. Internal fighting led to the gradual decline of the sultanate, and by the mid-19th century the town was a shadow of its former self.[2]

Some contend that Agadez was the furthermost extent of the Ottoman Empire on the African continent until the 19th century, before being occupied by the French colonial empire, though this claim has not been verified by historians.[3] The city was ruled by the French from 1906.[2] A rebellion by Kaocen Ag Mohammed occurred in 1916, but was defeated by French forces.[2] The French, unable to effectively administer this remote region, ruled semi-indirectly via a restored sultan.[2] Later, Agadez became an important location in the Tuareg Rebellion of the 1990s in central and northern Niger.

As a result of the Second Tuareg Rebellion, sporadic violence and the displacement of thousands of people affected the Agadez area from late 2007 into 2009. All of northern Niger was placed on the United States State Department list of areas which are unsafe for travel by United States citizens, covering late 2007 to the end of 2008.[4] Tourist flights to Agadez were suspended by European airlines for the 2007–2008 tourist season (September – March). The burgeoning tourist industry, which prior to 2007 had surpassed that of Niamey and the rest of the nation, essentially came to an end. The entire region was placed under a Nigerien government State of Exception (limiting travel, gatherings, political activities, etc.) in October 2007, renewed through early 2009. Roads to and from Agadez were reported to have been mined, and the government closed the area to international journalists and aid organizations. An unknown number (reported as several thousands) of internally displaced people converged on the city as a result of the unrest.

In the 2010s, Agadez became a major transit town for West African migrants heading to Libya and then on to Europe,[5] since Agadez is the final stop before passing through the long trek across the Sahara towards the Libyan coast.[6] Crackdowns in 2016 slowed the flow of migrants, but recent Displacement Tracking Matrix data showed a daily average of 1,212 individuals crossing at six monitored points in Niger,[7] many of whom would have been coming through Agadez. The city now hosts hundreds of migrants living in small houses on the outskirts of the city before moving on to Libya.[6]