Zika virus (ZIKV) is an arbovirus that caused widespread panic beginning in 2015 in northeastern Brazil due to the threatening link between infection and fetal abnormalities such as microcephaly, spontaneous abortions, and stillbirths. Since the epidemic began, the virus has been further investigated, unveiling that the long-term dangers of ZIKV infection go beyond fetal neurological impairment. Characterization of the active infection has proven difficult as only 20% of infected individuals are symptomatic. Additionally, ZIKV is often misdiagnosed due to serological cross-reactivity with similar flaviviruses such as dengue, yellow fever, and West Nile. To date, there is no approved vaccine or therapy against ZIKV, highlighting the urgent need to accurately identify active infection to help minimize the spread of the virus. Herein, we describe a highly specific and sensitive enzyme-linked immunosorbent assay to detect early active ZIKV using neutralizing human monoclonal antibodies isolated from infected patients in Brazil that do not cross-react with dengue viruses 1-4 and bind directly to a ZIKV immunodominant epitope. The calculated limits of detection of active ZIKV fall within the physiological ranges of the virus in human bodily fluids. This selective immunoassay creates the platform required for future translation toward a point-of-care assay for ZIKV, a necessity to diagnose active ZIKV in the remote regions of which it thrives.