Prenatal dexamethasone exposure (PDE) induces developmental toxicities of multi-organs and susceptibility to multi-diseases in offspring. However, the effects of PDE on osteoarthritis susceptibility in adult offspring and its mechanism have not been reported. In the present study, we treated pregnant Wistar rats with dexamethasone (0.2 mg/kg) daily on gestational days (GD) 9–20. Some pregnant rats were sacrificed on GD20, and the rest were delivered to obtain the postnatal offspring. The adult female offspring rats were performed with ovariectomy or sham operation during postnatal weeks 22–28. We found that PDE led to osteoarthritis phenotypes in articular cartilage and an increase in modified Mankin's score, but reduced the cartilage thickness in female adult offspring rats, which were more evident after ovariectomy. Moreover, PDE reduced the bone mass of subchondral bone in female adult offspring, which was aggravated by ovariectomy. The correlation analysis results indicated that the osteoarthritic phenotype and cartilage thickness were closely associated with the decreased bone mass of subchondral bone induced by PDE. Further, PDE retarded the development of primary and secondary ossification centers, then led to subchondral bone dysplasia, which could be partly mediated by the inhibited osteogenic function before and after birth. Collectively, the subchondral bone dysplasia partly participated in osteoarthritis susceptibility induced by PDE in female offspring rats.