Wide application of carbon dioxide (CO2) electrochemical energy storage requires catalysts with high mass activity. Alloy catalysts can achieve superior performance to single metals while reducing the cost by finely tuning the composition and morphology.. We used in silico quantum mechanics rapid screening to identify Au-Fe as a candidate improving CO2 reduction and then synthesized and tested it experimentally. The synthesized Au-Fe alloy catalyst evolves quickly into a stable Au-Fe core-shell nanoparticle (AuFe-CSNP) after leaching out surface Fe. This AuFe-CSNP exhibits exclusive CO selectivity, long-term stability, nearly a 100-fold increase in mass activity toward CO2 reduction compared with Au NP, and 0.2 V lower in overpotential. Calculations show that surface defects due to Fe leaching contribute significantly to decrease the overpotential.