This study examined the three-dimensional (3D) changes in craniofacial morphology between 482 identified Portuguese skulls from the eighteenth to the twentieth centuries and 150 modern Portuguese individuals randomly selected from the armed forces. The goal was to investigate the interrelationship between changes in various parts of the skull, in particular, the cranial base, the brain supporting structures, and the face. Cone beam computed tomography images from the identified skull collections belonging to the Department of Life Sciences at the University of Coimbra and Natural History National Museum of Lisbon were used. These 3D images from craniometric analyses included 19 different linear, angular, and orthogonal 3D measurements. The trend in horizontal position of the maxilla (SNA) and horizontal position of the mandible (SNB) angles showed a significant increase, while the relative position of the maxilla to mandible (ANB) and the global angle mean values decreased over time. Skulls from each subsequent century demonstrated a decrease in anterior cranial base, indicated by the mean distance between S and N landmarks. Significant negative correlations were found between SNA and anterior cranial base length (S-N). The negative correlations between SNB and anterior cranial base length (S-N) decreased from the eighteenth to nineteenth centuries. The twenty-first century skulls were characterized by a significant difference in the mean value of different craniofacial variables between males and females. The results of this study suggest changes in the 3D cephalometric measurements of craniofacial architecture. These changes are highly integrated, and show an interesting correlation between structures of the craniofacial facial complex and the anterior cranial base.