The spheno-occipital synchondrosis (SOS) in cranial base is an important growth center for the craniofacial skeleton, and also is a guide rail for development of the maxilla, midface, and mandible. Previous studies showed that SOS may be a treatment target for youngsters with midfacial hypoplasia and small cranial vault secondary to craniosynostosis. However, most of studies about the SOS are based on imaging data. In this study, we try to explore the characteristics of postnatal development of the mouse SOS based on histological analysis. Our findings showed that the width of the SOS in mice were gradually decreased from newborn mice to adult mice, and the SOS cartilage was gradually became small, then almost completely ossificated in adult mice. The resting and proliferative layers in SOS cartilage were gradually decreased, and almost only hypertrophic chondrocytes while no resting and proliferative layer chondrocytes in adult mice. The proliferative ability of SOS chondrocytes also gradually decreased. These findings will be of benefit for the further clinical treatment for patients with midfacial hypoplasia or small cranial vault secondary to craniosynostosis. Further evidence-based research about the clinical implication is necessary in future.