Abstract Standard petrographic, microthermometric and Raman spectroscopic analyses of fluid inclusions from the metamorphosed massive sulphide deposits at Ducktown, Tennessee, indicate that fluids with a wide range of compositions in the C–O–H–N–S–salt system were involved in the syn‐ to post‐metamorphic history of these deposits. Primary fluid inclusions from peak metamorphic clinopyroxene contain low‐salinity, H2O–CH4 fluids and calcite, quartz and pyrrhotite daughter crystals. Many of these inclusions exhibit morphologies resembling those produced in laboratory experiments in which confining pressures significantly exceed the internal pressures of the inclusions. Secondary inclusions in metamorphic quartz from veins, pods, and host matrix record a complex uplift history involving a variety of fluids in the C–O–H–N–salt system. Early fluids were generated by local devolatilization reactions while later fluids were derived externally.Isochores calculated for secondary inclusions in addition to the chronology of trapping and morphological features of primary and secondary fluid inclusions suggest an uplift path which was concave toward the temperature axis over the P–T range 6–3 kbar and 550–225° C. Immiscible H2O–CH4–N2–NaCl fluids were trapped under lithostatic to hydrostatic pressure conditions at 3–0.5 kbar and 215 ± 20° C. Entrapment occurred during Alleghanian thrusting, and the fluids may have been derived by tectonically driven expulsion of pore fluids and thermal maturation of organic material in lower‐plate sedimentary rocks which are thought to underlie the deposits. Episodic fracturing and concomitant pressure decreases in upper‐plate rocks, which host the ore bodies, would have allowed these fluids to move upward and become immiscible. Post‐Alleghanian uplift appears to have been temperature‐convex.Uplift rates of 0.10–0.05 mm year−1 from middle Ordovician to middle Silurian – late Devonian, and 0.07–0.12 mm year−1 from middle Silurian – late Devonian to late Permian are suggested by our uplift path and available geochronological data.