In this work, a mathematical model based on growth kinetics of microorganisms and substrates transportation through biofilms was developed to describe methane production and sulfate reduction with ethanol being a key electron donor. The model was calibrated and validated using experimental data from two case studies conducted in granule-based Upflow Anaerobic Sludge Blanket reactors. The results suggest that the developed model could satisfactorily describe methane and sulfide productions as well as ethanol and sulfate removals in both systems. The modeling results reveal a stratified distribution of methanogenic archaea, sulfate-reducing bacteria and fermentative bacteria in the anaerobic granular sludge and the relative abundances of these microorganisms vary with substrate concentrations. It also indicates sulfate-reducing bacteria can successfully outcompete fermentative bacteria for ethanol utilization when COD/SO42− ratio reaches 0.5. Model simulation suggests that an optimal granule diameter for the maximum methane production efficiency can be achieved while the sulfate reduction efficiency is not significantly affected by variation in granule size. It also indicates that the methane production and sulfate reduction can be affected by ethanol and sulfate loading rates, and the microbial community development stage in the reactor, which provided comprehensive insights into the system for its practical operation.