Hydrogen sulfide (H₂S) removal is a critical step in natural gas processing because of its adverse environmental, safety, and corrosion effects. This study evaluates and optimizes the performance of an industrial diethanolamine (DEA)-based gas sweetening unit at the Basrah Gas Company (BGC) using an integrated Aspen HYSYS simulation and statistical analysis framework. Response surface methodology (RSM) based on central composite design (CCD) was conducted to assess the influence of key operating variables, namely sour gas feed flow rate (7200–7700 kmol/hr), DEA concentration in the circulating solvent (25–35 wt.%), and excess DEA circulation (0.12–0.18) on H₂S removal efficiency response to reach the permitted pipeline specification (H₂S ≤ 55 ppmv). The highest H₂S removal efficiency (99.9233–99.9373%) was obtained, which corresponds to a treated-gas H₂S concentration of approximately 35.62–43.57 ppmv, indicating a meaningful compliance margin relative to the 55 ppmv limit. The core results indicate that DEA concentration is the dominant factor affecting H₂S removal efficiency more than the sour gas feed flow rate. Whereas, excess DEA circulation shows no statistically significant effect, referring to the fact that the process is not solvent-limited. The optimized operating conditions of 7700 kmol/hr, 35 wt%, and 0.18 achieve high H₂S removal efficiency of 99.9358% without requiring increased solvent circulation or major process modifications, providing practical guidance for operational optimization of industrial amine-based gas sweetening units.