In this study, the effect of three operating parameters, i.e., the first/second volumetric feeding ratio (milliliters/milliliters), the first anaerobic/aerobic (an/oxic) time ratio (minute/minute), and the second an/oxic time ratio (minute/minute), on the performance of a two-step fed sequencing batch reactor (SBR) system to treat swine wastewater for nutrients removal was examined. Central Composite Design, coupled with Response Surface Methodology, was employed to test these parameters at five levels in order to optimize the SBR to achieve the best removal efficiencies for six response variables including total nitrogen (TN), ammonium nitrogen (NH4-N), total phosphorus (TP), dissolved phosphorus (DP), chemical oxygen demand (COD), and biochemical oxygen demand (BOD). The results showed that the three parameters investigated had significant impact on all the response variables (TN, NH4-N, TP, DP, COD, and BOD), although the highest removal efficiency for each individual responses was associated with different combination of the three parameters. The maximum TN, NH4-N, TP, DP, COD, and BOD removal efficiencies of 96.38%, 95.38%, 93.62%, 94.3%, 95.26%, and 92.84% were obtained at the optimal first/second volumetric feeding ratio, first an/oxic time ratio, and second an/oxic time ratio of 3.23, 0.4, and 0.8 for TN; 2.64, 0.72, and 0.76 for NH4-N; 3.08, 1.16, and 1.07 for TP; 1.32, 0.81, and 1.0 for DP; 2.57, 0.96, and 1.12 for COD; and 1.62, 0.64, and 1.61 for BOD, respectively. Good linear relationships between the predicted and observed results for all the response variables were observed.