Background: Down syndrome (DS) is a genetic condition characterized by an extra copy of chromosome 21, resulting in various physical and cognitive features. This study aimed to comprehensively analyze the dental and craniofacial morphology of individuals with DS using Cone Beam Computed Tomography (CBCT). Methods: Six individuals with DS, comprising five males and one female aged 17 to 35 years, underwent CBCT scanning. Radiographic assessments included dentition, occlusion, paranasal sinuses, airway, skull bones, and suture calcification. Linear and angular cephalometric measurements were performed, and airway analysis was conducted using Dolphin 3D imaging software v.11. Results: The study revealed prognathic maxilla in five patients, prognathic mandible in four, and bimaxillary protrusion in two. Dental findings included microdontia, enamel hypoplasia, and congenitally missing teeth, with maxillary and mandibular third molars most commonly absent. Sinus abnormalities, delayed suture closure, and cervical spine anomalies were also observed. Conclusion: These findings contribute to a deeper understanding of DS-related craniofacial characteristics and emphasize the importance of considering these morphometric features in clinical management strategies for individuals with DS. This study's limited sample size underscores the significance of radiographic assessment in planning interventions such as cosmetic reconstructions, prosthetic rehabilitation, or orthodontic treatment for individuals with DS.