This paper discusses the hydrochemical evolution of groundwaters in the multilayer artesian aquifer of the Continental Intercalaire (the mainly Jurassic Agadez‐Dabla sandstones) aquifer of northern Niger. Isotopic and chemical changes in relation to the geological setting suggest that the increasing HCO3−alkalinity of the groundwaters is caused by interaction of deep CO2with the aquifer matrix. Alteration of feldspars by CO2with a δ13C value of −3.0‰ accounts for the observed alkalinity and isotopic and trends. Carbon 14 ages have been estimated for recent and Holocene groundwaters which have a distinct stable isotopic (2H and18O) signature compared with14C dead groundwaters from further west on the Irhazer Plain. Recharge temperatures, estimated by analysis of noble gas contents, show that the14C dead waters were recharged under conditions cooler than present averages in the region, possibly at the beginning of deglaciation (≈16 ka B.P.) or during the period 23–30 ka B.P. Trends in the hydrochemistry of U are related to the deep CO2alteration process. Radiogenic He contents increase along the flow direction and extremely high values occur in the proximity of U ores. Denitrification in the paleowaters of the Irhazer was assessed by measurements of nitrogen/