Co3O4 is an attractive alternative to precious metal catalyst for CO oxidation due to its low cost and earth abundance, but its high catalytic activity is severely degraded in the presence of water. Here, we show that doping La into Co3O4 surfaces significantly enhances CO oxidation activity under moisture-rich condition. While bare Co3O4 is deactivated under moisture, the La-doped Co3O4 catalysts exhibit greatly improved activity and water resistance. The higher ratio of active Co3+ on the La-doped Co3O4 surface results in the enhanced activity. Especially, the La doping greatly reduces the formation of surface OH on the Co3O4 surface, which causes the poor water resistance. Density functional theory calculations reveal that the La doping suppresses the vacancy-assisted dissociative adsorption of H2O, resulting in less formation of surface OH and thereby mitigating water poisoning on the Co3O4 surface. This work can provide an insight into the surface restructuring for highly active and water-resistant Co3O4 catalysts.