A dozen uranium occurrences are known in the Western Zambian Copperbelt (Domes region, Zambia). The host-rocks, Neoproterozoic kyanite ± talc micaschists, have been interpreted as meta-evaporites that formed part of an epicontinental sequence affected by upper amphibolite metamorphism during the Pan-African orogeny. Ca-Na metasomatism, expressed by the presence of apatite, epidote and scapolite, is regionally extensive in the Katanga and the pre-Katanga rocks in the Domes region. The present study focuses on the Solwezi dome in the Western Zambian Copperbelt. Two distinct uranium mineralization events that took place here mark the transition from crustal-thickening by tectonic accretion to exhumation of the metamorphic host rocks. U-Pb dating of uraninite and Th-Pb dating of monazite show that the first U-mineralization event took place between ~ 550 Ma and ~ 530 Ma. The event is therefore contemporaneous with crustal thickening and, on the basis of fluid inclusion analyses, can be related to circulation of hypersaline Ca-rich metamorphic fluids trapped at minimum P-T conditions of 460 MPa and 500 °C. On a regional scale, the event is related to an epidote-apatite metasomatic assemblage. The second mineralization event, dated at between ~ 510 and ~ 500 Ma by Th-Pb dating of monazite, is related to high-salinity Ca-Na-rich metamorphic fluids and occurred during exhumation of the high-grade metamorphic rocks. These fluids were trapped at the ductile/brittle transition at 150 to 260 MPa and 200 to 300 °C. A regional-scale scapolitization is attributed to these late fluid circulations. These fluid-rock interactions, described at the regional scale, are also characterized at the mineral scale. Alteration reactions, assisted by CaCl2-rich fluids, indicate that monazite and allanite hosted by the pre-Katanga rocks potentially acted as U sources for these Pan-African synmetamorphic uranium mineralizations.