The number of significant issues on many welding processes are often connected to high productivity and manufacturability at low costs. The research on welding processes in the literature has reported several research activities, but there is still scope for improvement in most industrial settings. The primary goal of this research is to determine the best super-TIG welding settings to use for groove welding. First, in order to determine the quality characteristics and risks associated with them, concepts and frameworks of quality by design (QbD) which is a new standard in pharmaceutical area in order to improve drug qualities were integrated into this process optimization. Second, stepwise experimental design approaches including a factorial design as well as a response surface methodology (RSM) were customized and performed for this specific automated super-TIG welding process. Third, based on experimental design results, the optimal operating conditions with both design space (i.e., acceptable range of operating conditions) and safe operating space (i.e., safe range of operating conditions) were obtained. Finally, a case study including QbD steps, stepwise experimental design approaches, design and operating spaces, the optimal factor settings, and their association validation results was conducted for verification purposes.