Anaerobic digestion is considered unsuitable for the bioremediation of tannery effluent due to process inhibition, mainly due to high concentrations of sulfur species, and the accumulation of H2S and/or NH3. This study using the standardized biochemical methane potential protocol showed that efficient processing is possible with slaughterhouse wastewater, provided sufficient functional biomass is present at the start of the process and the SO42− concentration is below inhibition threshold. Methanogenic activity (K = 13.4–17.5 and µm = 0.15–0.27) and CH4 yields were high when reactors were operated ISR ≥ 3 and/or lower SO42− ≤ 710 mg/L while high SO42− ≥ 1960 mg/L and ISR < 3.0 caused almost complete inhibition regardless of corresponding ISR and SO42−. The theoretical optimum operating conditions (922 mg/L SO42−, ISR = 3.72) are expected to generate 361 mL biogas/gVS, 235 mL CH4/gVS with reduction efficiencies of 27.5% VS, 27.4% TS, 75.1% TOC, 75.6% SO42−, and 41.1% COD. This implies that tannery sludge will be reduced by about 27% (dry mass) and SO42− by 76%, with a fraction of it recovered as S0. The models displayed a perfect fit to the cumulative CH4 yields with high precision in the order Logistic > Cone > modified Gompertz > first order.

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