Objective To explore the effect of facial asymmetry on stress distribution in temporomandibular joints (TMJs) for mandibular prognathism patients by three-dimensional finite element analysis. Methods Eight 3D maxillofacial models were established in MIMICS based on cone-beam CT of 4 mandibular prognathism patients with asymmetry and 4 mandibular prognathism patients without asymmetry. Muscle forces and boundary conditions corresponding to the unilateral occlusion (unilateral molar chewing) were applied on the models in ABAQUS. The maximum principal stress and the minimum principal stress of TMJ were chosen for analysis. Results There were significant differences of the maximum and minimum principal stresses at the condyles between the mandibular prognathism patients with and without facial asymmetry under unilateral occlusions (P<0.05). Compared to the patients without facial asymmetry, the stresses on the condyle in the patients with asymmetry increased by 2~3 times, and the stresses on articular fossa increased 5~7 times. Among the mandibular prognathism patients with asymmetry, the stresses of the ipsilateral TMJ in the patients with temporomandibular disorder (TMD) were significantly higher than those in the patients without TMD. Conclusions Facial asymmetry increased the stresses of the articular fossa and condyle in the mandibular prognathism patients. And TMD caused greater stress in the ipsilateral TMJ of the mandibular prognathism patient with asymmetry. Therefore, different treatment strategies should be considered for mandibular prognathism with facial asymmetry.