<p>This study investigates the milling behavior and surface quality of heat-treated Al-Li, Al-Li-Cu, and Al-Li-Cu-Sc alloys, focusing on the effects of feed rate, cutting speed, material hardness, and lubrication conditions. Al-Li alloys, known for their low density and high strength, are widely used in aerospace applications. The addition of copper and scandium further alters the alloys’ microstructure and mechanical properties, influencing their response to machining. A full factorial Design of Experiments (DOE) approach was applied to systematically study the combined influence of machining parameters, material composition, and heat treatment. Surface roughness was measured and analyzed using statistical tools such as ANOVA to identify significant factors and interactions. Results indicate that feed rate has the most significant impact on surface roughness, followed by hardness and lubrication. Higher cutting speeds generally improve surface roughness, while wet machining enhances surface finish for alloys with lower hardness. The findings offer valuable guidelines for optimizing milling processes of Al-Li alloys to achieve superior surface quality, contributing to more efficient and cost-effective manufacturing of lightweight, high-performance aerospace components. The interactions between feed rate, cutting speed, and cooling mode have significant effects on the machined surface roughness.</p>