Craniofacial asymmetry, mandibular condylar modeling and temporomandibular joint disorders are common comorbidities of skeletally disproportionate malocclusions, but etiology of occurrence together is poorly understood. We compared asymmetry, condyle modeling stability and temporomandibular health in a cohort of 128 patients having orthodontics and orthognathic surgery to correct dentofacial deformity malocclusions. We also compared ACTN3 and ENPP1 genotypes for association to clinical conditions. Pre-surgical posterior-anterior cephalometric and panometric radiographic analyses; jaw pain and function questionnaire and clinical examination of TMD; and SNP-genotype analysis from saliva samples were compared to assess interrelationships. Almost half had asymmetries in need of surgical correction, which could be subdivided into four distinct morphological patterns. Asymmetric condyle modeling between sides was significantly greater in craniofacial asymmetry, but most commonly had an unanticipated pattern. Often, longer or larger condyles occurred on the shorter mandibular ramus side. Subjects with longer ramus but dimensionally smaller condyles were more likely to have self-reported TMD symptoms (p = 0.023) and significantly greater clinical diagnosis of TMD (p = 0 .000001), with masticatory myalgia most prominent. Genotyping found two significant genotype associations for ACTN3 rs1671064 (Q523R missense) p = 0.02; rs678397 (intronic SNP) p = 0.04 and one significant allele association rs1815739 (R577X nonsense) p = 0.00. Skeletal asymmetry, unusual condyle modeling and TMD are common and interrelated components of many dentofacial deformities. Imbalanced musculoskeletal functional adaptations and genetic or epigenetic influences contribute to the etiology, and require further investigation.