Distillers corn oil (DCO), a byproduct of corn ethanol production, offers an alternative glyceride source for biodiesel production. Nonetheless, its higher free fatty acids (FFA) content compared to other vegetable oils hampers its direct conversion into fatty acid methyl esters (FAME) due to soap formation, catalysts' activity decreasing, and emulsions generation (thus reducing FAME yield), which compromise the quality and stability of the biodiesel produced. Thus, pretreatment steps such as esterification may reduce the FFA to mitigate these issues. In this context, by utilizing glycerine, a solution emerges: esterifying these high‐acidity oils to convert FFA into triglycerides (TAG) before transesterification. However, little is known about how integrated reaction conditions can affect the process in a catalyst‐free system. Thus, our study was guided by a clear‐cut objective: transforming DCO into a raw material ideally suited for biodiesel production, which involved a dramatic reduction in FFA content, reducing it from 18% to a mere 2% while preserving a high concentration of TAG. For that, we systematically employed a response surface methodology with a three‐factorial central composite design to investigate the complex interactions among key parameters: temperature, vacuum pressure, and the glycerol/oil mass ratio. Elevated temperatures and a 2:1 glycerol/oil mass ratio were beneficial for FFA reduction, increased TAG content, and improved oil color. Interaction analysis identified synergistic temperature and vacuum pressure effects on FFA reduction, TAG production, and photometric color index reduction, revealing optimal conditions. Hence, the statistical model highlights DCO as a viable oil for future transesterification processes, laying the foundation for an eco‐friendly and economically efficient biodiesel production network.