Aluminum alloys are widely used in the automotive and aerospace industries due to their lower mass-to-strength ratio than other metallic alloys. Apart from their inherent properties, aluminum alloys like other metallic alloys show a significant change in their mechanical properties according to the machining parameters. The research literature on obtaining optimum mechanical properties of aluminum alloys that undergo machining is very limited. Moreover, the combined effect of several parameters on the machinability of aluminum alloys has not yet been explored. In this paper, the effect of three machining parameters (Depth of Cut (DoC)), feed rate (FR), and cutting speed (CS) on the subsurface damage and fatigue life of aerospace-grade aluminum alloy (Al-6082-T6) is observed. Samples are prepared using a full fractional approach to effectively capture the effect of all input parameters. Thereafter, samples were subjected to surface roughness, micro-hardness, and fatigue life tests. Results of surface roughness and micro-hardness tests are compared with fatigue life. The general linear model was employed to capture the percentage effect of each input parameter on the output parameters. The results showed that DoC was the main contributing factor that caused subsurface damage, while surface roughness and fatigue life were mainly affected by FR and CS. Optical microscope images showed a white layer formation that had higher hardness than the base metal. Overall, this research work proposes the input parameters that can be used to achieve minimum surface damage and fatigue life.