To realize highly sensitive SAW devices, novel Al–Cu thin films were developed using a combinatorial sputtering system. The Al–Cu sample library exhibited a wide range of chemical compositions and electrical resistivities, providing valuable insights for selecting optimal materials for SAW devices. Considering the significant influence of electrode resistivity and density on acoustic wave propagation, an Al–Cu film with 65 at% Al was selected as the IDT electrode material. The selected Al–Cu film demonstrated a resistivity of 6.0 × 10−5 Ω-cm and a density of 4.4 g/cm3, making it suitable for SAW-based microfluidic actuator applications. XRD analysis revealed that the Al–Cu film consisted of a physical mixture of Al and Cu without the formation of Al–Cu alloy phases. The film exhibited a fine-grained microstructure with an average crystallite size of 7.5 nm and surface roughness of approximately 6 nm. The SAW device fabricated with Al–Cu IDT electrodes exhibited excellent acoustic performance, resonating at 143 MHz without frequency shift and achieving an insertion loss of −13.68 dB and a FWHM of 0.41 dB. In contrast, the Au electrode-based SAW device showed significantly degraded acoustic characteristics. Moreover, the SAW-based microfluidic module equipped with optimized Al–Cu IDT electrodes successfully separated 5 μm polystyrene (PS) particles even at high flow rates, outperforming devices with Au IDT electrodes. This enhanced performance can be attributed to the improved resonance characteristics of the SAW device, which resulted in a stronger acoustic radiation force exerted on the PS particles.