A high-temperature vapor-fed direct methanol fuel cell (DMFC) has been implemented using H3PO4-doped polybenzimidazole (PBI) as the electrolyte. The influence of the cell temperature, the methanol concentration, and the oxygen partial pressure has been studied. This investigation included the evaluation of the cell performance, each electrode potential, and crossover current. A lifetime test for 10 days was intermittently carried out to assess the stability of the cell response. Increases in the temperature notably enhanced the performance of the cell, although the methanol crossover also increased. The methanol concentration was found to have an optimum value, because a low amount of methanol led to mass-transfer limitations and a large amount promoted the crossover and limited the availability of water for methanol oxidation. An increase in the oxygen partial pressure markedly improved the cell response. The higher comburent availability and reduced methanol crossover effect explain this behavior. The study of the combined effect of the oxygen partial pressure and methanol concentration confirmed this effect. The preliminary durability results showed quite stable performance for the cell at a constant current density of 100 mA cm−2. Finally, a comparison between PBI and the traditional DMFC membrane (Nafion) was carried out. This comparison showed the PBI-based cell to be a good candidate for DMFC.