Approximately 10% of copper resources in the Central African Copperbelt, the world’s largest, sediment-hosted stratiform copper province, occur in the Domes region of northwestern Zambia. The copper deposits and prospects are commonly hosted by amphibolite-facies metamorphic rocks and lie within or adjacent to several basement inliers. Minor molybdenite accompanies the copper-iron sulfide minerals in two deposits and four prospects within the Mwombezhi dome as well as in deposits elsewhere in the Domes region. The results of Re-Os dating of 11 molybdenite samples reveal the existence of two discrete copper-mineralizing epochs, separated by >500 m.y. Most of the mineralization, including that in the Chimiwungu orebody at Lumwana, the largest deposit in the Mwombezhi dome, formed within a maximum interval of ~42 m.y. (538.9–497.1 Ma), which spans the peak of the Lufilian collisional orogeny. In contrast, three samples (four determinations) from the Nyungu prospect returned Mesoproterozoic ages of 1084 to 1059 ± 5 Ma, coincident with the Irumide collisional orogeny. Although several investigators have speculated that the copper in the Central African Copperbelt deposits was extracted from the basement, this is the first unambiguous evidence for an appreciable copper concentration of pre-Katangan (pre-Neoproterozoic) age. Based on this evidence, additional Mesoproterozoic and possibly even older copper concentrations seem likely to exist elsewhere beneath and/or alongside the Copperbelt in both Zambia and the Democratic Republic of Congo. Such preenrichment of the basement in copper may have contributed to the enormous metal endowment of the Central African Copperbelt.