Previous studies on Athabasca basin unconformity-related uranium deposits have focused on major deposits and have not investigated sites with barren alteration systems that could clarify some of the critical factors controlling mineralization processes. A paragenetic study of the Wheeler River area reveals the presence of minerals that formed during the diagenetic, the main hydrothermal, which is subdivided into early, mid-, and late hydrothermal substages, and the late alteration stages. The diagenetic stage consists of early quartz overgrowths, siderite, rutile, hematite, and abundant dickite in the pore spaces of the Manitou Falls Formation. The early hydrothermal alteration substage is characterized by pervasive 1Mc muscovite alteration and minor goyazite clusters, which formed from oxidizing basinal fluids at temperatures around 240°C prior to 1550 Ma, based on Ar-Ar dates. The mid-hydrothermal alteration substage comprises dravite and sudoite in the basal 200 m of the Manitou Falls Formation, which are interpreted to have formed at temperatures around 175°C from fluids chemically distinct but isotopically similar to the basinal fluids involved during the early hydrothermal alteration substage. The late hydrothermal substage was observed only at zone K of the Wheeler River area and is characterized by the precipitation of clinochlore, copper sulfides, and florencite from reducing basement fluids emerging into the Manitou Falls Formation at temperatures around 230°C, creating a ~250-m-high by ~250-m-wide reducing halo. Oxidized uranium-bearing basinal fluids interacted with the Manitou Falls Formation during the early hydrothermal substage prior to the arrival of the reducing fluids during the mid- and late hydrothermal substages and this precluded uranium precipitation. The post-hydrothermal alteration stage is characterized by formation of kaolinite after late hydrothermal clinochlore near fractures by meteoric waters. A minimal amount of leachable radiogenic Pb, with a Pb-Pb model age of 1907 Ma that is older age than both the Athabasca basin and the main mineralization event of 1590 Ma, was encountered at zone K, indicating low probability of this area to host uranium mineralization. However, areas of possible unconformity-related uranium deposits were identified outside zone K wherein significant amounts leachable radiogenic Pb were observed.