Ultrasonic testing is a promising alternative quality inspection technique to the expensive microscopic imaging to characterize metal matrix nanocomposites. However, due to the complexity of the wave–microstructure interaction, and the difficulty in fabricating nanocomposites of different microstructural features, it is very challenging to build reliable relationships between ultrasonic testing results and nanocomposites quality. In this research, we propose a microstructure modeling and wave propagation simulation method to simulate ultrasonic attenuation characteristic for A206–Al2O3 metal matrix nanocomposites (MMNCs). In particular, a modified Voronoi diagram is used to reproduce the microstructures and the numeric method elastodynamic finite integration technique (EFIT) is used to simulate the wave propagation through the generated microstructures. Linear mixed effects model (LME) is used to quantify the between-curve variation of ultrasonic attenuation from both experiment and simulation. Permutation test is employed to quantify the similarity of the quantified variation between experiment and simulation. This research supports the experimental results through the simulation approach and provides a better understanding of the relationship between attenuation curves and the microstructures.