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The Tim Mersoï uranium province in northern Niger is one of the world’s largest uranium reserves and fourth-highest uranium producer. The main uranium deposits (Arlit, Akouta, and Imouraren) are located in continental siliciclastic formations. The regional north–south-trending fault (the Arlit Fault) strongly controls them, as well as secondary discontinuity networks oriented NNE-SSW, ENE-WSW, and WNW-ESE. The Arlit and Akouta uranium-ores are hosted in reduced Carboniferous formations and occur as reduced U4+ phase mineralizations. Besides, the Imouraren deposit is hosted by an oxidized Jurassic formation with a predominance of U6+ silicate and vanadate minerals and relics of reduced mineralization. New U-Pb SIMS data have been obtained on the three deposits, and the results reveal two main stages of uranium deposition and ore metallogenesis. (i) the 90–145 Ma Lower Cretaceous mineralization is related to a significant tectonothermal event, synchronous with the Atlantic rifting that induced the deformation and brine migration from Triassic formations. Primary uraninite and chalcocite are formed by fluid mixing in a reduced environment at that stage at a depth of 1 km at less at a temperature 115–150 °C, hotter than that of the reservoir. (ii) During later Cenozoic exhumation of the basin, a series of remobilizations of primary uranium stock resulted in the formation of much younger uraninites under reduced conditions at Arlit-Akouta around 50 Ma. At Imouraren, younger uraninites formed between 34 and 8 Ma under locally reduced conditions, and were followed by secondary U-minerals from 21 Ma up to 3–1.6 Ma during supergene events. These ages are close or superimposed with the main oxidation stages, affecting West Africa during the Cenozoic, and attest of water table oscillations.