Significance: Atomic-level in situ environmental transmission electron microscopy observation of the dynamic activation process on a low-indexed CuAu surface under water–gas shift reaction (WGSR) condition has been revealed. The atomic-scale structural activation of a CuAu surface features a gas-dependent periodic surface restructuring and elemental ordering, explaining the “synergy effect” from the structural point of view. These real-time changes under relevant reactant gases and temperature are correlated with the reaction route of WGSR corroborated by density functional theory–based calculation and ab initio molecular dynamics simulation and can provide insights for atom-precision catalyst design.