Low crossover of both methanol and water through a polymer membrane in a direct methanol fuel cell (DMFC) is essential for using high concentration methanol in portable power applications. A novel design of the membrane-electrolyte assembly (MEA) has been developed in this work to attain low methanol crossover, low water crossover, and high cell performance simultaneously. The anode catalyst layer, in the form of a catalyzed diffusion medium (CDM), serves as a methanol diffusion barrier to reduce methanol crossover. In addition, a highly hydrophobic cathode microporous layer (MPL) is employed to build up the hydraulic pressure at the cathode and hence drive the product water from the cathode into the anode to offset the water dragged by electro-osmosis. The new MEA, consisting of a CDM anode, a thin Nafion membrane, and a carbon cloth precoated with an MPL on the cathode, is shown to attain: (i) a net water transport coefficient through the membrane smaller than 0.8 at and 0.4 at ; (ii) fuel efficiency of ; and (iii) a steady-state power density of at ca. and with low stoichiometric flow rates of ambient dry air and methanol solution.