Megaesophagus is a diffuse or focal esophageal hypomotility disorder attributed to either a myopathy, neuropathy, or junctionopathy with a broad range of potential etiologies. The differential diagnoses are discussed as it relates to a case of a 5 year old, mixed-breed dog with megaesophagus, cranial neuropathy, and progressive myopathy. A presumptive diagnosis of Neosporosis was made, and despite treatment, the patient later developed generalized muscle atrophy. Biopsies of the affected muscles were taken revealing an immune-mediated polymyositis, a sequela attributed to previous infection with Neospora caninum. The pathogenesis of Neosporosis as it contributes to the patient’s clinical presentation, its role in the development of immune-mediated polymyositis, as well as the management of chronic megaesophagus and polymyositis is discussed.