Periodic density functional theory (DFT) calculations and microkinetic modeling are used to investigate the electrochemical oxidation of H-2 fuel on the (001) surface of Sr2Fe1.5Mo0.5O6 (SFMO) perovskite under anodic solid oxide fuel cell conditions. Three surface models with different Fe/Mo ratios in the topmost layer-identified by ab initio thermodynamic analysis-are used to investigate the H-2 oxidation mechanism. A microkinetic analysis that considers the effects of anode bias potential suggests that a higher Mo concentration in the surface increases the activity of the surface toward H-2 oxidation. At operating voltage and anodic SOFC conditions, the model predicts that water desorption is rate-controlling and that stabilizing the oxygen vacancy structure increases the overall rate for H-2 oxidation. Although we find that Mo plays a crucial role in improving catalytic activity of SFMO, under fuel cell operating conditions, the Mo content in the surface layer tends to be very low. On the basis of these results and in agreement with previous experimental observations, a strategy for improving the overall electrochemical performance of SFMO is increasing the Mo content or adding small amounts of an active transition metal, such as Ni, to the surface to lower the oxygen vacancy formation energy of the SFMO surface.