Abstract: Objective 1Cr21Ni5Ti duplex stainless steel possesses a suite of superlative mechanical properties, such as high strength, high toughness, exceptional corrosion resistance, and good weldability, thereby demonstrating extensive potential for application in numerous industrial fields. For the welding technology of thick-walled duplex stainless steel structures, powder pool coupled activated TIG (PPCA-TIG) method offers significant advantages. It achieves greater weld penetration than that of conventional TIG and supports process automation. This paper aims to optimize weld penetration in PPCA-TIG. Methods This experiment employed response surface methodology for optimization design. Two key factors, welding current and welding speed, were selected, and a regression model was established based on experimental data. Results The optimization result established the optimal welding parameters as 235.39 A welding current and 67.53 mm/min travel speed, resulting in a predicted weld penetration of 7.874 mm. Moreover, P-value of the model was lower than 0.0001 and lack-of-fit was 0.3130, which validated that the regression model was robust, provided a good fit throughout the design domain, and was reliable for the prediction and analysis of weld penetration. Conclusion An examination of the test results further revealed that welded joints fabricated under the optimized welding parameters possessed a high-quality microstructure and correspondingly excellent mechanical properties.