Sulfidation is a widely used technology to improve the floatability of oxidized metal minerals or to stabilize the heavy metals in various wastes. The sulfidation mechanism of ZnO with pyrite was detailedly studied by thermodynamic calculation and roasting experiments. The sulfidation behaviors, phase transformations, microscopic morphology and surface properties were investigated by TG-DSC, ICP, XRD, SEM-EDS, and XPS analysis. The results indicate that the nature of the sulfidation is the reaction of ZnO with the gaseous sulfur generated by the decomposition of pyrite. Pyrite instead of sulfur as the sulfidizing agent can not only relieve the volatilization loss of sulfur but also enhance the formation of liquid phase and thus facilitate the growth of ZnS particles. The sulfidation reaction belongs to surface chemical reaction and relates to the migration of oxygen from the inside of ZnO to its surfaces. The presence of carbon not only eliminates the release of SO2, but also decreases the decomposition temperature of pyrite and promotes the sulfidation of ZnO. The addition of Na2CO3 promotes the sulfidation of ZnO at lower temperatures (below 850 °C) and enhances the growth of ZnS particles but has a negative effect on the sulfidation at higher temperatures.