Operating a direct methanol fuel cell (DMFC) with ultra-low fuel stoichiometry is desirable to build a compact portable power system. Through 3D computational modeling with statistical analysis, severe non-uniformity of fuel concentration leading to high methanol crossover in the inlet region and poor fuel supply in the outlet region is predicted under ultra-low fuel stoichiometry condition, which causes large voltage loss or even cell shut-down. After identifying controlling parameters of methanol transport, this paper proposes streamline-graded structures (SGS) of the anode channel to mitigate anode fuel distribution non-uniformity and to boost cell performance and fuel efficiency together. Computational results show that streamline-graded structures achieve about 10% of voltage gain and 3% of fuel efficiency improvement compared to the conventional DMFC design by mitigating anode non-uniformity. (C) 2013 Elsevier B.V. All rights reserved.