A mathematical model was developed to evaluate the effect of the common fuel additive ethanol on benzene fate and transport in fuel-contaminated groundwater and to discern the most influential benzene plume elongation mechanisms. The model, developed as a module for the Reactive Transport in 3 Dimensions (RT3D) model, includes commonly considered fate and transport processes (advection, dispersion, adsorption, biodegradation, and depletion of molecular oxygen during biodegradation) and substrate interactions previously not considered (e.g., a decrease in the specific benzene utilization rate due to metabolic flux dilution and/or catabolite repression) as well as microbial population shifts. Benzene plume elongation predictions, based on literature model parameters, were on the order of 40% for a constant source of E10 gasoline (10% vol/vol ethanol), which compares favorably to field observations. For low benzene concentrations (<1 mg/L), oxygen depletion during ethanol degradation was the principal mechanism hindering benzene natural attenuation. For higher benzene concentrations (exerting an oxygen demand higher than the available dissolved oxygen), metabolic flux dilution was the dominant plume elongation process. If oxygen were not limiting, as might be the case in zones undergoing aerobic biostimulation, model simulations showed that microbial growth on ethanol could offset negative substrate interactions and enhance benzene degradation, resulting in shorter plumes than baseline conditions without ethanol.