Mathematical modeling strategies have been developed to quantitatively describe the degradation behavior of porous polyesters by considering both pore-structure characteristics and the "reaction-diffusion" mechanism. The degradation kinetic parameters of poly(lactide-co-glycolide) (PLGA) and poly(DL-lactic acid) (PDLLA) are obtained by fitting degradation data of the corresponding solid plates. For the degradation of porous polyesters with randomly distributed pores, the effect of porosity on the effective diffusion coefficient has been taken into account. The increase of porosity slows down the autocatalytic reaction as well as the whole degradation process by enhancing the diffusion coefficient of oligomers. The effect of porosity is gradually weakened because the increase of diffusion rate is retarded with a further increase of porosity. Varied effects of porosity on the degradation of polyesters with a wide dimensionless noncatalytic rate and diffusion rate have also been simulated. For the degradation of porous polyesters with open pores, a pore-wall size distribution (PSD) modeling strategy is developed with the assumption that the diffusion path of oligomers is dependent on the size distribution of pore walls, and this modeling strategy can be further simplified with an equivalent pore-wall size. Both the developed modeling strategies have been validated by the degradation behavior of elaborately designed PLGA and PDLLA foams with different pore morphologies, which are valuable for the degradation prediction and structure design of porous polyester devices.