Abstract Objectives This study aimed to investigate the three-dimensional (3D) mandibular asymmetry in craniofacial microsomia (CFM) and its association with the Pruzansky–Kaban classification system. Materials and methods Cone-beam computed tomography images of 48 adult CFM cases were collected. The asymmetry of the mandibular body and ramus was analyzed with 3D landmarks. The mirrored mandibular model was registered on the original model, yielding a color-coded distance map and an average distance (i.e., asymmetry score) to quantify the overall mandibular asymmetry. Results The lengths of the mandibular body and ramus were significantly shorter on the affected than the contralateral side (p < 0.001). The ANB (p = 0.009), body and ramal lengths (both p < 0.001), and body and ramal length asymmetry (both p < 0.05) were significantly different between mild (types I/IIA) and severe (types IIB/III) cases. The mandibular asymmetry score correlated with mandibular body length asymmetry (r = 0.296, p = 0.046). CFM mandibles showed high variability in shape asymmetry. Conclusions CFM patients showed distinct body and ramal length asymmetries. In severe cases, mandibles were smaller, more retruded, and more asymmetric in length. The mandibular shape asymmetry was highly variable regardless of the Pruzansky–Kaban types, being a determinant in the extent of overall mandibular asymmetry. Clinical relevance The 3D morphologic analysis provides better insights into real mandibular asymmetry. Although the Pruzansky–Kaban classification was applied, high individual variability of the mandibular morphology still existed within the types. Therefore, individualized analyses and treatment plans for CFM patients are highly recommended.