Faults are mostly considered as low-permeability zones due to their frequent sealing, but they can also contribute significantly to fluid movements in sedimentary basins, and subsequently to temperature anomalies. In favorable cases, paleo-temperatures and pressures can be determined from fluid-inclusion and chlorite thermometry. Using this approach, we estimate the temperature gap between incoming fluids and host rocks along the Arlit Fault, a major fault affecting the whole series of continental siliciclastic formations from Paleozoic to Late Jurassic in the Tim Mersoï Basin (Niger). Strong alteration halos and uranium deposits occur along this regional north–south-trending fault, as well as a secondary network of NE–SW faults. Sandstone porosity is partially reduced by authigenic quartz and Fe-rich trioctahedral chlorites. The chlorites precipitated directly from the solutions under reducing conditions, prior to uranium-oxide deposition. The temperatures and pressures are estimated to be around 115–150 °C and 80–120 bars respectively, and are remarkably similar in all formations from the Carboniferous to the Jurassic. These temperatures are much higher, around 60–80 °C, than those estimated at maximum burial, and document hot fluid flow along the major fault. This thermal anomaly is inferred to be related to the opening of the Atlantic Ocean during the Cretaceous, before the onset of the main exhumation stages during the mid-Tertiary. This study documents the role of faults as significant conduits for fluid flow, and their role in the mass and heat transfer related to the formation of economic deposits.