<p>Copper smelting slag tailings are characterized by the presence of various toxic heavy metals, which pose a risk of environmental contamination when stored in open air. This study investigates the stabilization effectiveness and mechanisms of sulfate-reducing bacteria (SRB) utilizing either phosphogypsum (PG) or flue gas desulfurization gypsum (FGDG) as a sulfur source for the immobilization of copper (Cu), lead (Pb), and zinc (Zn) in copper smelting slag tailings. The results indicated that the bioavailability reduction rates (i.e., stabilization effectiveness) of Pb and Zn in the copper smelting slag tailings initially increased and subsequently decreased with the increasing amount of PG or FGDG, while the change in Cu was not significant. Notably, PG was determined to be a more effective sulfur source for SRB. At a PG addition level of 15%, the bioavailability reduction rates for Cu, Pb, and Zn in the copper smelting slag tailings were found to be 90.41%, 94.27%, and 85.00%, respectively. Additionally, the oxidizable and residual fractions of Cu, Pb, and Zn in the copper smelting slag tailings increased following stabilization. Within the mixed systems, the oxidation–reduction potential (ORP) exhibited a significant decline over time, while the pH level increased, and the concentrations of Cu decreased marginally. Analyses conducted using SEM–EDS, XRD, FTIR, XPS, and 16S rRNA sequencing revealed that the formation of metal sulfides contributed to the reduction of bioavailability of Cu, Pb, and Zn in the copper smelting slag tailings. Furthermore, the residual calcium sulfate dihydrate (CaSO₄·2H₂O) from PG or FGDG was shown to provide a sustained supply of sulfur for SRB activity. In conclusion, this study offers valuable insights for the remediation of Cu, Pb, and Zn in similar smelting slag tailings and highlights the potential for the comprehensive utilization of typical industrial by-product gypsum.</p>