"We have already triggered an alert warning the population to be prepared and vigilant: flood surges have already carried off an ambulance with two people inside," the city's mayor said.
Agadez and its 145,000 residents face the threat of surging waters from Kori-Telwa, a seasonal waterway that can become swiftly supercharged with runoff from the Air Mountains.
The old town of Agadez which dates back to the 15th and 16th centuries is classified by UNESCO as being of "outstanding universal value".
It includes a well-preserved group of palatial and religious buildings, including a 27-metre (88.5-feet) -high minaret made entirely of mud brick.
On Tuesday, two people died when a building housing a mosque and a school collapsed in the city, emergency services said.
Floods have already killed 22 people nationwide, destroyed homes and gardens and decimated livestock.
"The Kori carries a lot of water, it takes everything down in its path, and finds it way to the city," described the local online news site Air Info.
The rainy season is currently in full swing in Niger.
Despite its short duration of no more than three months, the country has faced recurring floods in recent years in a state where poor harvests are usually caused by drought.
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