Purpose <p>An abnormal lingual frenulum is an important risk factor for obstructive sleep apnea (OSA). This study evaluated the potential role of craniofacial characteristics in the predisposition of a short lingual frenulum and reduced tongue mobility in the development of OSA.</p> Methods <p>This cross-sectional, case-control study recruited participants with and without OSA. Craniofacial and frenulum measurements were obtained using photogrammetry. Tongue mobility was evaluated by measuring tongue range of motion ratio. Mediation analysis was performed to determine whether the effect of the lingual frenulum on OSA could be explained by craniofacial disharmony.</p> Results <p>Data from 222 eligible participants were included, of whom 44% had confirmed OSA and exhibited shorter lingual frenula and retrognathic mandibles. After adjusting for age, body mass index, and sex, a shorter lingual frenulum and reduced tongue mobility were correlated with a larger retroposition distance (<i>r</i>=-0.18, <i>p</i> = 0.0.1, and <i>r</i>=-0.22, <i>p</i> = 0.01, respectively), smaller mandibular subnasion angle (<i>r</i> = 0.15, <i>p</i> = 0.03, and <i>r</i> = 0.14, <i>p</i> = 0.02, respectively), and smaller mandibular triangle area (<i>r</i> = 0.17, <i>p</i> &lt; 0.01, and <i>r</i> = 0.18, <i>p</i> = 0.01, respectively). The relationship between tongue mobility and the apnea–hypopnea index (AHI) was mediated by retroposition distance (indirect effect, -0.54; percent mediated, 60.43%) and mandibular triangle area (indirect effect, -5.57; percent mediated 66.79%) in more than one-half of the entire cohort.</p> Conclusions <p>Shorter lingual frenulum length and lower tongue mobility were associated with a relatively small retrognathic mandible in participants with and without OSA. More than one-half of the increase in AHI was attributed to reduced tongue mobility, possibly mediated by an undeveloped mandible.</p>