Poly(ester-imide)s (PEIs) are considered the most promising polymers for space exploration attributed to their flexibility, low-density, and outstanding mechanical behaviors. Nevertheless, their atomic oxygen (AO) degradation effects pose a significant challenge for PEI films deployed in low Earth orbit (LEO). In this study, we examined the structural evolution behaviors and AO degradation mechanisms of the PEI by integrating exposure tests with reactive molecular dynamics (ReaxFF-MD) simulation. The PEI exhibited linear AO erosion kinetics, characterized by a constant erosion yield (Ey) of -1.1 x 10-24 cm3 atom- 1. Morphological analysis revealed the ascending surface roughnesses and shaggy topographies as AO fluence increased. Spectroscopic investigations demonstrated that the extensive elimination of specific sites (C=O, C-O-C, C-N, C-H, and C-C groups) and the release of volatile species (H2O, COx, and NOx) were the priority consequences of AO erosion. In addition, the AO-exposed PEI demonstrated the gradual declines in hydrophobicity and transparency. Moreover, the ReaxFFMD simulation aligned with the experimental results, further corroborating the rationality of the collision enhanced erosion reaction mechanism.