A numerical model was applied to investigate sequential biodegradation of dissolved benzene, toluene, and xylene (BTX) within a fractured aquifer system under the presence of multiple electron acceptors and microbes. The present model differs from existing biodegradation models in fractures by adopting the dual-porosity conceptualization in the model formulation. The influence of fracture-matrix (F-M) interactions on the biodegradation rate of dissolved BTX within a fractured rock was examined. Aerobic, denitrifying, and sulfate reduction biodegradation reactions of BTX constituents were considered to occur within the fractured rock system. Model results suggested that the biodegradation greatly reduces the migration length of dissolved BTX along directions parallel and perpendicular to fracture length. The biodegradation rate of benzene in fracture and matrix was more influenced by the injection rate of dissolved oxygen and aerobic microbe at the fracture inlet. However, the biodegradation rate of toluene and xylene was more under anaerobic biodegradation conditions. A sensitivity analysis was conducted to analyze the sensitivity of flow, fracture, and matrix parameters on the concentration distribution of BTX, electron acceptors, and biomass within the F-M system.