We investigated the optimum flow channel design for direct methanol fuel cells (DMFCs). Especially, we explored the effect of the pressure drop across the inlet and outlet on the performance of the DMFCs with various flow channel designs. In DMFC systems, the optimization of such parameters are critical to minimize the power usage by the auxiliary devices, such as fuel pump and blowers. In this paper, we present how the pressure drop control may determine the optimal driving point of the DMFC stack. Also, we show how the optimal fuel utilization ratio may be achieved, without degrading the performance of DMFC stacks. Overall, we discuss how the flow channel design affects the selection of the balance of plant (BOP) components, the design of the DMFC system, and the efficiency of the entire system.