Research on increasing the power density per unit volume by removing and miniaturizing the balance of plants to operate proton exchange membrane fuel cells (PEMFCs) is essential. For drone applications, it is critical to reduce the weight of the PEMFC system. Therefore, the cathode compressor and humidifier are typically removed by directly using atmospheric air, and this operating method is called an open-cathode (OC). However, in the case of the OC-PEMFC, research has not been actively conducted compared to the PEMFC operating using the conventional method. In this study, the effects of various experimental variables on the OC-PEMFC performance are investigated. First, the effects of the flow rate of fans, whether the fan is used or not, operating temperature, humidification of hydrogen, and direction of the cathode opening area on the OC-PEMFC performance are systematically investigated. Second, the effects of substrate thickness of the gas diffusion layer, adding hydrophilic carbon black to the microporous layer, and perforations in the gas diffusion layer, one of the main components in the PEMFC, on the OC-PEMFC performance are identified. Finally, the shapes of endplates that prevent the accumulation of generated water in the cathode opening area are proposed.