Gamma-ray spectrometer measurements were obtained at and in the vicinity of 104 of the 124 U, Th, Mo, and rare-earth-element (REE) occurrences examined in the Central Metasedimentary Belt of the Grenville Province. Spatial, temporal, mineralogical, and geochemical relationships among granitic pegmatites, phlogopite – scapolite – Ca pyroxene skarns, and fluorite – apatite – calcite veins hosting U, Th, Mo, and REE minerals indicate a common magmatic–hydrothermal origin. Quartz–feldspar gneisses in the Central Metasedimentary Belt (n = 54) have low abundances of uranium (1–7 ppm) and thorium (4–27 ppm) suggesting that partial melting, fractional crystallization, and volatile phase separation were responsible for the enrichment of uranium (2–37 ppm) and thorium (5–102 ppm) in uncontaminated granitic pegmatites (n = 163) derived during ultrametamorphism. The U/Th ratio is probably inherited from the source quartz–feldspar gneiss protolith and enhanced during fractionation.Average U and Th concentrations and U/Th ratios at numerous localities show significant positive correlations among pegmatites, skarns, and veins, providing further evidence for a related origin. The interaction of the pegmatite-derived hydrothermal fluids with host rocks produced a spectrum of types and styles of alteration, which include (i) hybridization and (or) endoskarnification along pegmatite margins; (ii) marble- and clinopyroxenite-hosted exoskarn; and (iii) fluorite–apatite–calcite veins. The deposition of U, Th, Mo, and REE from the evolving hydrothermal fluid is responsible for the heterogeneous distribution of U, Th, and REE minerals and molybdenite within pegmatites, skarns, and veins at each locality. Secondary enrichment of uranium in association with hematitized sheared pegmatites and veins may be responsible for the observed large variation in U/Th ratios at some sites.