The process design of sequencing batch reactors (SBR) based on mathematical modeling is complex because of the unsteady nature of the process and the large number of kinetic and stoichiometric parameters involved. This paper proposes a model-based design methodology that uses a mathematical model with fewer parameters for removal of organic and nitrogen substrates in the SBR. The resulting mathematical model has been calibrated and validated before its use in model-based design. The data for model calibration and validation were obtained from the operation of a full-scale 836 m 3 /h (5.3 mgd) SBR system at the City of Tahlequah, Oklahoma. A calibration methodology also was presented to determine unknown kinetic and stoichiometric parameters using an optimization technique called simulated annealing. Model-based design reduced the total volume of the reactor by approximately 11% from the existing design. It also eliminated 0.92 hours of cycle time and 1.07 hours of aeration time per cycle, which would result in a total energy savings of $11,640 per year for the 836 m 3 /h (5.3 mgd) SBR system. Water Environ. Res., 82, 462 (2010).