The pattern of expansion of endodontic lesions in the jaws has been less commonly addressed in the literature. For this reason, the aim of this study is to assess the pattern of endodontic lesions of maxillary and mandibular posterior teeth using cone-beam computed tomography (CBCT). This cross-sectional study was conducted on 317 endodontic lesions of posterior teeth on CBCT scans retrieved from a radiology center in Qazvin, Iran, from 2020 to 2022. Endodontic lesions were assessed on sagittal, coronal, and axial sections by an endodontist and dental student using the Romexis software. The largest lesion diameter was measured occluso-apically, mesiodistally, and buccolingually. Lesion size was analyzed based on age, gender, jaw, tooth type, and presence/absence of root filling by independent samples t-tests and a one-way Analysis Of Variannce (ANOVA). The largest diameter of lesions in the maxilla and mandible was recorded in the occluso-apical dimension followed by buccolingual and mesiodistal dimensions (p > 0.05). The pattern of lesions was the same in teeth with and without endodontic treatment, but it was significantly different in maxillary and mandibular endodontically treated teeth in the occluso-apical and buccolingual dimensions (p < 0.05). No significant correlation was noted with tooth type or jaw except for maxillary and mandibular first molar lesions, which were significantly different in the occluso-apical dimension (p < 0.05). Lesion size in all three dimensions was significantly greater in males than females (p < 0.05), and was the highest in the occluso-apical dimension in both genders. In the maxilla, the mean lesion size significantly decreased in the mesiodistal dimension with age (p < 0.05). In conclusion, the largest lesion diameter in the maxilla and mandible was found in the occluso-apical dimension, indicating the role of bone density in the pattern of lesions.