Low dose and accessibility have increased the application of cone beam computed tomography (CBCT). Often serial images are captured for patients to diagnose and plan treatment in the craniofacial region. However, CBCT images are highly variable and lack harmonious reproduction, especially in the head’s orientation. Though user-defined orientation methods have been suggested, the reproducibility remains controversial. Here, we propose a landmark-free reorientation methodology based on principal component analysis (PCA) for harmonious orientation of serially captured CBCTs. We analyzed three serial CBCT scans collected for 29 individuals who underwent orthognathic surgery. We first defined a region of interest with the proposed protocol by combining 2D rendering and 3D convex hull method, and identified an intermediary arrangement point. PCA identified the y-axis (anterioposterior) followed by the secondary x-axis (transverse). Finally, by defining the perpendicular z-axis, a new global orientation was assigned. The goodness of alignment (Hausdorff distance) showed a marked improvement (> 50%). Furthermore, we clustered cases based on clinical asymmetry and validated that the protocol was unaffected by the severity of the skeletal deformity. Therefore, it could be suggested that integrating the proposed algorithm as the preliminary step in CBCT evaluation will address a fundamental step towards harmonizing the craniofacial imaging records.