Zika virus (ZIKV) is a mosquito-borne flavivirus with a significant public health impact highlighted by the ongoing epidemic in the Americas. We describe a 44-year-old male presenting to our tropical medicine center with complaints of fever, headache, joint pain, and rash after recent travel to Guyana. The patient subsequently developed gait imbalance and lower extremity weakness with clinical examination, cerebrospinal fluid studies, and magnetic resonance imaging of the spine consistent with a diagnosis of Guillain-Barre syndrome (GBS). ZIKV infection was confirmed via detection of ZIKV RNA in urine by polymerase chain reaction. The patient was treated with intravenous immunoglobulin and experienced near-complete neurologic recovery, reporting ongoing mild paresthesia up to 2 months later. This case highlights the diagnostic challenges posed by ZIKV and underscores the need for clinician awareness of the potential for neurological complications such as GBS with ZIKV infection.