Microfluidic fuel cells exploit the lack of convective mixing at low Reynolds number to eliminate the need for a physical membrane to separate the fuel from the oxidant. Slow transport of reactants in combination with high catalytic surface-to-volume ratios often inhibit the efficiency of a microfluidic fuel cell. The performance of microfluidic devices that rely on surface electrochemical reactions is controlled by the interplay between reaction kinetics and the rate of mass transfer to the reactive surfaces. This paper presents theoretical and experimental work to describe the role of flow rate, microchannel geometry, and location of electrodes within a microfluidic fuel cell on its performance. A transport model, based on the convective-diffusive flux of reactants, is developed that describes the optimal conditions for maximizing both the average current density and the percentage of fuel utilized. The results show that the performance can be improved when the design of the device includes electrodes smaller than a critical length. The results of this study advance current approaches to the design of microfluidic fuel cells and other electrochemically-coupled microfluidic devices.