Synergistic sulfidation roasting of heavy metal gypsum residue and secondary zinc oxide fume was proposed by using the research idea of “waste to treat waste”. Thermodynamic studies indicated that the sulfidation of zinc oxide could be effectively enhanced by increasing the dosage of calcium sulfate and carbon powder in the range of 500−800 °C. The synergistic sulfidation experiments of heavy metal gypsum residue with secondary zinc oxide showed that the sulfidation rate of zinc reached 90.39% and the grain size of ZnS increased from 5 to 10 μm under the conditions of temperature 700 °C, carbon powder 30%, Na₂CO₃ 10%, mass ratio of gypsum residue to secondary zinc oxide 1.4꞉1, roasting time 2 h and cooling rate 1 °C/min. Meanwhile, 76.32% F, 72.11% Cl and 93.41% As were removed. TG/DTG−DSC, 3D FTIR spectra and SEM analysis showed that the conversion of CaSO₄ to CaCO₃ and the avoidance of CO₂ and SO₂ production were achieved under optimized conditions. This study achieves efficient sulfidation of zinc as well as growth of ZnS grains, laying the theoretical and technological foundation for subsequent recovery of ZnS by flotation.