The intracratonic Paleoproterozoic Nonacho Basin, deposited on the western margin of the Rae craton, contains historic polymetallic (i.e., U, Cu, Fe, Pb, Zn, Ag) occurrences spatially associated with its unconformable contact with underlying crystalline basement rocks and regionally occurring faults. This study presents the paragenesis, mineral chemistry and geochemistry of uranium mineralized rocks and minerals of the MacInnis Lake sub-basin of the Nonacho Basin, to evaluate the style and relative timing of uranium mineralization. Mineralization is restricted to regionally occurring deformation zones, and post-dates widely spread and pervasive albitization and more local Ba-rich K-feldspar alteration of host rocks. Uranium mineralized rocks show elevated concentration of Cu, Ag and Au relative to variably altered host rocks. Microscopic and compositionally heterogeneous altered uraninite occurs (i) as overgrowths on partially dissolved Cu-sulphides with magnetite in chlorite ± quartz, calcite veins, and (ii) with minor uranophane in hematite-sericite-chlorite ± quartz breccia and stockwork. Both uraninite types are Th poor (<0.09 wt.% ThO2) and variably rich in SO4 (up to 2.26 wt.%), suggesting a low-temperature hydrothermal origin in a relatively oxidized environment. Rare-earth element (+Y) concentrations in type-i uraninite are high, up to 9.5 wt.% Σ(REE+Y)2O3 with CeN/YN values > 1, similar to REE compositions of uraninite in metasomatic iron and alkali-calcic systems (MIAC), including low-temperature hematite-type IOCG-deposits (e.g., Olympic Dam, Gawler Craton, Australia) and albitite-hosted uranium deposits (e.g., Southern Breccia, Great Bear Magmatic Zone, Canada, and Gunnar Deposit, Beaverlodge District, Canada). Both uraninite types are variably rich in Ba (up to 3 wt.% BaO), a geochemical marker for MIAC systems, provided by the dissolution of earlier secondary Ba-rich K-feldspar. Chemical U-Th-Pb dating yields minimum ages of 1757 to 1739 ± 70 Ma for type-ii uraninite-uranophane, consistent with strike-slip movement along regional structures of the basin. We suggest that MacInnis Lake uranium occurrences formed from oxidized hydrothermal fluids along previously altered (albitized, potassically altered) regional-scale faults. Uranium minerals precipitated on earlier Fe-rich sulfides (chalcopyrite, bornite), which acted as a redox trap for mineralization, in low-temperature (~310–330 °C, based on Al-in-chlorite thermometry) breccias and stockwork zones, late in a metasomatic iron and alkali-calcic alteration system.