High-performance acoustic-damping flexible polyurethane foams (FPUFs) were fabricated using synthesized linear saturated aliphatic polyesters, methylene diphenyl diisocyanate, and other reagents by one-shot bulk polymerization (isocyanate index = 110 and water content = 5%). In this study, the effect of the chemical structure of different LSAPs on microphase separation and acoustic dampening behavior of FPUFs was investigated using atomic force microscopy, Fourier transform infrared spectroscopy, compressive strength, optical microscopy, and an impedance tube device. The results revealed that by increasing the microphase separation, sound absorption efficiency increased up to 45%. Also, by increasing microphase separation, compressive strength, open-cell contents, roughness, and cell size distribution of FPUFs increased, and the average cell size decreased. Sound wave energy dissipation of FPUFs can be explained by the synergistic actions of the microphase separation including the viscoelastic behavior of segments and increasing of drainage flow pathway. Finally, the results revealed that soundproofing FPUFs under optimum conditions for microphase separation and drainage flow can be promising candidates for use as sound-insulating materials. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46744. © 2018 Wiley Periodicals, Inc.