The combined effect of ultrasonic vibration (UT) and applied pressure (P) on the microstructure and mechanical properties of the as-cast Al-5.0Cu-0.6Mn-0.6Fe alloy was investigated by using optical microscope (OM), scanning electron microscope (SEM) coupled with energy dispersive X-ray (EDX), image analysis as well as tensile test. The results showed that the P+UT processing has an siginificant effect on the morphology and size of α-Al, Fe-rich intermetallics, and Al₂Cu, which promotes the morphology of α-Al transformation from dendritic to globular structure and significantly reduces the size of α-Fe, Al₆(FeMn), and Al₂Cu phase. The P+UT processing is helpful to reduce the degree of bimodal structure which usually occurrence under applied pressure and reduce the segregation along the grain boundary. The best as-cast tensile properties produced by the P+UT processing were ultimate tensile strength (UTS): 268 MPa, yield strength (YS): 192 MPa, and elongation: 17.1%, which were 64%, 59%, and 307% higher than those of the non-treated alloy, respectively.