Creutzfeldt-Jakob disease (CJD) is the most common human prion disease presenting with subacute cognitive decline. Common MRI findings for CJD include the T2 prolongation signal of the putamen and head of caudate. Diffusion-weighted MRI (DW-MRI) is considered to be the most sensitive technique for the detection of CJD-related abnormalities, especially for cortical changes. We report the case of a 77-year-old female who presented with dizziness, visual hallucination, and a rapid decline in her mental state shortly after a right knee surgery. Brain MRI with contrast showed cortical and subcortical T2 fluid-attenuated inversion recovery (FLAIR) hyperintensities in bilateral posterior temporal lobes and the left occipital lobe without an associated enhancement, suggestive of posterior reversible encephalopathy syndrome (PRES). Workup including metabolic, infectious, and vasculitic panels were all within normal limits. A few days later, she developed persistent myoclonus, and a continuous electroencephalogram (EEG) revealed multifocal epileptiform and generalized discharges, forming multifocal periodic discharges and generalized periodic discharges (GPDs). Cerebrospinal fluid (CSF) analysis was positive for 14-3-3 and elevated T-tau protein consistent with a diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). This is a rare case of CJD presenting with a brain MRI resembling PRES. CJD may have various features on MRI, and a high degree of suspicion is required to confirm the diagnosis.