The Zambian Copperbelt is arguably the most significantly mineralized Neoproterozoic basin on Earth, preserving a truly spectacular scale of mineralization: in excess of 1 × 109 t of ore at ∼2.7% copper has been extracted to date, and there are also major cobalt accumulations. The origin of these deposits has been hotly debated for more than six decades, yet the driving forces that generated this system are poorly understood, in particular the relationships between tectonics, paleo–fluid circulation, and ore deposition. We present new field and isotopic data for the Nchanga deposits in which the bulk of the mineralization is hosted by shale-capped feldspathic arenites and arkoses that have undergone recrystallization and hydrothermal alteration within a host-rock package controlled by low-angle thrust faults. By using in situ laser combustion, we show for the first time that the range of δ34S for copper-cobalt ore sulfides (−1‰ to +18‰) cannot have the same source as diagenetic pyrite (−1‰ to −17‰). We suggest a new epigenetic model for the formation of these spectacular Nchanga orebodies that involves the introduction of metal- and sulfate-bearing hydrothermal fluids into quartzofeldspathic units during basin inversion, with sulfide derived from thermochemical reduction of the sulfate near the site of deposition.