As a critical component for attenuating noise radiation in turbofan engine nacelles, the performance optimization of acoustic liners plays a decisive role in achieving aviation airworthiness certification. With the prevailing trend toward high-bypass-ratio configurations in turbofan engine design, the inherent conflict between axially constrained nacelle space and enhanced noise suppression efficacy has become increasingly pronounced. This study systematically investigates the acoustic performance of spatially topology-optimized inlet acoustic liners through multiscale validation. Initially, the spatial optimization methodology and noise reduction mechanisms of inlet acoustic liners were systematically elucidated. Subsequently, component-level impedance extraction experiments were conducted to validate the acoustic impedance model employed in the optimized design. Furthermore, acoustic mode testing on representative-scale liners substantiated the enhanced noise suppression mechanisms inherent to spatially optimized configurations. Ultimately, full-scale validation was performed using a spinning mode synthesizer to quantify the optimized liner’s noise abatement performance. Experimental findings conclusively demonstrated that spatial optimization significantly improved the acoustic suppression capability: a 5 dB enhancement compared to conventional uniform liner configurations, and an 18 dB superiority relative to full-scale circumferentially segmented counterparts.