Highly crystallized polylactic acid (PLA) is suitable for industrial applications due to its stiffness, heat resistance, and dimensional stability. However, crystal lamellae in PLA products might delay PLA decomposition in the environment. This study clarifies how the initial crystal structure influences the hydrolytic degradation of PLA under accelerated conditions. Crystallized PLA was prepared by annealing amorphous PLA at a specific temperature under reduced pressure. Specimens with varied crystal structure were kept at 70 °C and in a relative humidity (RH) of 95% for a specific time. Changes in crystal structure were analyzed using differential calorimetry and wide-angle X-lay diffraction. The molecular weight (MW) was measured with gel permeation chromatography. The crystallinity of the amorphous PLA became the same as that of the initially annealed PLA within one hour at 70 °C and 95% RH. The MW of the amorphous PLA decreased faster even though the crystallinity was similar during the accelerated degradation. The low MW chains of the amorphous PLA tended to decrease faster, although changes in the MW distribution suggested random scission of the molecular chains for initially crystallized PLA. The concentrations of chain ends and impurities, which catalyze hydrolysis, in the amorphous region were considered to be different in the initial crystallization. The crystallinity alone does not determine the speed of hydrolysis.