Although the upflow anaerobic sludge blanket (UASB) reactor has been widely applied for domestic wastewater treatment in many developing countries, there is no sufficient mathematical model for proper design and operation of the reactor. An empirical model based on non-linear regression was developed to represent the physical and chemical removal of suspended solids (SS) in the reactor. Moreover, a simplified dynamic model based on ADM1 and the empirical model for SS removal was developed for anaerobic digestion of the entrapped SS and dissolved matter in the wastewater. The empirical model showed that effluent suspended chemical oxygen demand (CODss) concentration is directly proportional to the influent CODss concentration and inversely proportional to both the hydraulic retention time (HRT) of the reactor and wastewater temperature. For obtaining sufficient CODss removal, the HRT of the UASB reactor must be higher than 4 h, and higher HRT than 12 h slightly improved CODss removal. The dynamic model results showed that the required time for filling the reactor with sludge mainly depends on influent total chemical oxygen demand (CODt) concentration and HRT. The influent CODt concentration, HRT and temperature play a crucial role on the performance of the reactor. The results indicated that shorter HRT is needed for optimization of CODt removal, as compared with optimization of CODt conversion to methane. Based on the model results, the design HRT of the UASB reactor should be selected based on the optimization of wastewater conversion and minimization of biodegradable SS accumulation in the sludge bed, not only based on COD removal, to guarantee a stable reactor performance.