The West Nile virus (WNV) belongs to the genus of flaviviruses and is known to cause irreversible neurologic deficits. Neuroinvasive WNV cases continue to be rare and have a higher prevalence in South America, Africa, and Asia. Here we report a 55-year-old female from North America who presented with acute-onset encephalopathy, fever, myalgias, and Anton syndrome. Neuroradiographic findings included diffuse white matter abnormalities of both cortical and subcortical structures and the patient was diagnosed with posterior reversible encephalopathy syndrome (PRES). Further workup revealed WNV antibodies in both cerebrospinal fluid (CSF) and serum. Management of WNV encephalitis continues to be poor and thus the patient was referred to a long-term care facility. Furthermore, Anton syndrome is a rare focal neurologic deficit that has never been previously associated with the WNV. This case aims to highlight the epidemiology of WNV in the United States, the mechanisms of WNV encephalitis, and an overview of Anton syndrome.