There is great interest in developing edible films (EFs) with functional properties made from renewable resources to solve environmental problems associated with plastic waste and improve food preservation and safety. Corn starch is the main raw material employed for producing EFs due to its biodegradability, and availability. Nonetheless, the hydrogen bonding interactions of the native starch structure are strong, limiting its use in the development of bioplastics. In addition, starch-based materials are hydrophilic and lack mechanical integrity. A measure to overcome these disadvantages is the starch native structure modification by a reactive extrusion, where acetylation is one of the most applied chemical modifications. The functionality of acetylated modified corn starch is determined by the degree of substitution (DS). Glycerol is a widely used plasticizer in the food area and is essential in forming starch-based EFs, improving their flexibility and elongation. Hence, this research aimed to develop acetylated modified corn starch edible films (AcEFs) with a DS (0–0.2) and Glycerol Content (GC) (15–30%) to improve its functional properties. The acetylated modified corn starch was obtained by reactive extrusion. The casting technique was used to obtain AcEFs; these were characterized and optimized, evaluating the deformation, puncture resistance, carbon dioxide permeability, water vapor permeability, and water solubility. The data was analyzed using the surface response methodology, and the optimization was carried out using the numerical method. According to the optimization study, the AcEFs with the best mechanical and barrier properties were obtained with 0.16 DS and 18.30% GC.