Background: The skull is a complex structure formed by the craniofacial bones’ elaborate organization. The growth pattern in each craniofacial bone of the postnatal skull has been presented in wild-type mice. However, the skull’s growth pattern, determined by the craniofacial bones’ coordinated growth, is unfamiliar. This study aimed to examine the overall morphological change in the mid-sagittal plane of the postnatal mice’s skulls and interaction between the craniofacial bones. Methods: Geometric morphometric principal component analysis was performed in the mid-sagittal plane of 31 wild-type mice’s skulls from postnatal days 28 to 98. The relationship between the cranial base and cranial vault was investigated by comparing skulls with early fusion and non-fusion of intersphenoid synchondrosis (ISS). Results: The cranial vault flattening and sphenoid bone length increased with age. The cranial vault curvature and sphenoid base length showed a positive correlation that was confirmed by comparing the skulls with early fusion and non-fusion of ISS. The sphenoid bone length and cranial vault angle significantly decreased in the skulls with early fusion of ISS compared to non-fusion skulls. Conclusions It is suggested that the cranial vault flattening is sphenoid bone length-induced but cranial vault length-independent during postnatal mice skull development.