Uranium (U) deposits can undergo oxidizing events, subsequent to which the U may be redistributed or precipitated under distinct mineralogical forms. Occurrences of U6+ minerals can be the result of either (i) in situ oxidation and alteration of previous U4+ minerals or (ii) direct precipitation from U6+-rich solutions. Samples from Imouraren, the largest U6+ore deposit known in the world, located in the Tim Mersoï Basin, Northern Niger, have been studied to determine the nature, distribution, and timing of occurrences of U and related minerals. The host rock is composed of sandstones and analcime-rich siliciclastic rocks of Jurassic age. The U ore is largely dominated by acicular hexavalent U minerals and by a very small amount of uraninite. A comprehensive geochemical model that describes the origin and geochemical setting of this style of economically important mineralization has been developed. The petrographic and mineralogical studies show evidence of in situ uraninite alteration into uranophane and metatyuyamunite, documented by textural relationships and chemical analyses using SEM and electron microprobe. The textural relationship between the U4+ and U6+ minerals is supported by the near-identical REE signatures of the primary uraninite and related secondary U minerals. Ion microprobe U-Pb dating (from 21 to ~ 1 Ma) confirms that primary uraninites were altered to U6+ minerals under supergene conditions during Cenozoic oxidation events in western Africa, in relation with the well-known stages of intense continental weathering that have affected western Africa from the early Cenozoic to recent times.