The Coles Hill uranium deposit, with an indicated resource of about 130 Mlb of U3O8, is the largest unmined uranium deposit in the United States. The deposit is hosted in the Taconian (approx. 480–450 Ma) Martinsville igneous complex, which consists of the Ordovician Leatherwood Granite (granodiorite) and the Silurian Rich Acres Formation (diorite). The host rock was metamorphosed to orthogneiss during the Alleghanian orogeny (approx. 325–260 Ma), when it also underwent dextral strike-slip movement along the Brookneal shear zone. During the Triassic, extensional tectonics led to the development of the Dan River Basin that lies east of Coles Hill. The mineralized zone is hosted in brittle structures in the footwall of the Triassic Chatham fault that forms the western edge of the basin. Within brittle fracture zones, uranium silicate and uranium-bearing fluorapatite with traces of brannerite form veins and breccia-fill with chlorite, quartz, titanium oxide, pyrite, and calcite. Uranium silicates also coat and replace primary titanite, zircon, ilmenite, and sulfides. Sodium metasomatism preceded and accompanied uranium mineralization, pervasively altering host rock and forming albite from primary feldspar, depositing limpid albite rims on igneous feldspar, altering titanite to titanium oxide and calcite, and forming riebeckite. Various geothermometers indicate temperatures of less than ~200°C during mineralization. In situ U-Pb analyses of titanite, Ti-oxide, and apatite, along with Rb/Sr and U/Pb isotope systematics of whole-rock samples, resolve the timing of geologic processes affecting Coles Hill. The host Leatherwood Granite containing primary euhedral titanite is dated at 450 to 445 Ma, in agreement with previously obtained ages from zircon in the Martinsville igneous complex. A regional metamorphic event at 330 to 310 Ma formed anhedral titanite and some apatite, reequilibrated whole-rock Rb/Sr and U-Pb isotopes, and is interpreted to have coincided with movement along the Brookneal shear zone. During shearing and metamorphism, primary refractory uranium-bearing minerals including titanite, zircon, and uranothorite were recrystallized, and uranium was liberated and mixed locally with hematite, clay, and other fine-grained minerals. Uranium mineralization was accompanied by a metasomatic episode between 250 and 200 Ma that reset the Rb-Sr and U-Pb isotope systems and formed titanium oxide and apatite that are associated and, in places, intimately intergrown with uranium silicate dating mineralization. This event coincides with rifting that formed the Dan River Basin and was a precursor to the breakup of Pangea. The orientation of late-stage tectonic stylolites is compatible with their formation during Late Triassic to Early Jurassic basin inversion, postdating the main stage of uranium mineralization and effectively dating mineralization as Mesozoic. Based on the close spatial and temporal association of uranium with apatite, we propose that uranium was carried as a uranyl-phosphate complex. Uranium was locally reduced by coupled redox reactions with ferrous iron and sulfide minerals in the host rock, forming uranium silicates. The release of calcium during sodium metasomatic alteration of primary calcic feldspar and titanite in the host rock initiated successive reactions in which uranium and phosphate in mineralizing fluids combined with calcium to form U-enriched fluorapatite. Based on the deposit mineralogy, oxygen isotope geochemistry, and trace element characteristics of uranium silicate and gangue minerals, the primary mineralizing fluids likely included connate and/or meteoric water sourced from the adjacent Dan River Basin. High heat flow related to Mesozoic rifting may have driven these (P-Na-F-rich) fluids through local aquifers and into basin margin faults, transporting uranium from the basin or mobilizing uranium from previously formed U minerals in the Brookneal shear zone, or from U-enriched older basement rock.