Polyhalogenated carbazoles (PHCZs) are a kind of emerging contaminants which have widespread distribution, strong potential persistence, high bioaccumulation, and dioxin-like toxicity. In this study, we used sulfidated zero-valent iron (S-ZVI) synthesized by ball-milling to activate peroxydisulfate (PDS) for the degradation of 1,3,6,8-tetrabromocarbazole (1,3,6,8-BCZ). The initial 1 mg/L 1,3,6,8-BCZ was degraded by 92.9 % within 30 min in S-ZVI/PDS system. The pseudo-first-order rate constant was estimated as high as 0.182 min⁻¹. Electron paramagnetic resonance (EPR) study and quenching experiments results revealed that •OH, ¹O₂, O₂^•−, and SO₄^•− played roles in the degradation of 1,3,6,8-BCZ, with their contribution percentages of 32.8 %, 32.5 %, 24.8 % and 9.9 %, respectively. By further density functional theory (DFT) calculations, radical addition by •OH and 1,4-cycloaddition by ¹O₂ were suggested as the dominant channels for 1,3,6,8-BCZ degradation, while O₂^•− exerted an indirect synergistic influence. Based on the identification of intermediates and analysis of Fukui indices, 1,3,6,8-BCZ degraded through three degradation pathways, namely hydroxylation, debromination, and C–N bond cleavage. The S/Fe molar ratio, S-ZVI dosage, PDS dosage, reaction temperature, initial pH, and water matrices had influences on the degradation in 1,3,6,8-BCZ, result in a great toxicity reduction. Overall, this research developed an effective and feasible approach for the treatment of PHCZs, and which gave deep insights into the vital roles and synergistic effects of various reactive species based on the combination of experimental study and theoretical calculation.