Akabane virus is a teratogenic pathogen transmitted by Culicoides spp. to ruminants. The virus induces anomalies in the central nervous system in the developing fetus, resulting in arthrogryposis-hydranencephaly (A-H) syndrome. During three outbreaks of the disease (2002, 2013, and 2020), 77 calves were born in Varamin, Iran, with A-H syndrome. The presenting neurologic signs were categorized into three main groups, as common, less common, and uncommon signs. The common signs were unawareness of the surroundings, blindness, deep depression, partial failure of suckling, and unintelligent behavior. The less commonly noted signs were hyperexcitability, regurgitation, head pressing, compulsive walking, and kicking, while the uncommon signs comprised protrusion of the tongue, making sounds resembling barking, carnivore-like milk drinking, and deafness. Arthrogryposis, dome-shaped skull, kyphosis, torticollis, lordosis, scoliosis, and spina bifida were the diagnosed skeletal defects. Upon necropsy, hydranencephaly, hydrocephaly, and microencephaly were seen in the calves presenting neurologic signs, while astrocytosis, astrogliosis, focal gliosis, perivascular, perineuronal, and submeningeal edema, perivascular cuffing, non-suppurative meningitis, non-suppurative encephalitis and lymphoplasmacytic infiltration, and perivascular and parenchymal hemorrhage were seen in samples obtained from the brains. RT-PCR detected Akabane virus in the brain tissues of the affected calves. This is the first clinical study of Akabane disease in calves in Iran.