Oxidative coupling of alcohols is of great practical importance due to the wide range of synthetic applications using esters. Controlling the selectivity toward production of specific esters in cross-coupling is a long-sought goal in designing efficient synthetic routes. We report a quantitative study of the factors that determine the esterification selectivity in the oxidative cross-coupling of alcohols mediated by oxygen-covered Au(111). The high reactivity of gold is attributed to the activity of atomic oxygen bound to Au particles in forming surface-bound alkoxy species. The relative surface concentrations of alkoxys and the ease of the β-H elimination play critical roles in determining the product distribution. For a given reactant composition the surface concentration of alkoxys is skewed toward the higher molecular weight alcohol in the mixture exposed to the surface. Vibrational spectroscopic studies reveal that the relative stabilities of alkoxys parallel the gas phase acidities of the corresponding alcohols, in agreement with other coinage metal surfaces. Further, the activation energies for β-H cleavage of alkoxys are found to follow the descending order: E(methoxy) > E(ethoxy) > E(butoxy). The combination of these factors optimizes cross-coupling in a reactant mixture containing an excess of the lower molecular weight alcohol. The excellent match of product distribution between our low-pressure, single-crystal study and that observed for atmospheric pressure, liquid-phase reactions over supported gold catalysts provides strong evidence that the mechanistic insights gained from fundamental surface science study can serve as guiding principles in controlling selectivity under realistic catalytic conditions.