We present a highly active CeO2‐based catalyst for oxidizing CO in automobile exhaust. This catalyst was systemically designed by co‐doping with transition metals (TMs). First, we used density functional theory (DFT) calculations to screen Mn and 13 dopant TMs (periods 4∼6 in groups VIII∼XI) and their 91 binary combinations for co‐doping. As a result, Cu and (Cu, Ag) were found to be the best candidates among the single and binary dopants, respectively. Next, we synthesized CeO2 nanoparticles doped with Cu or (Cu, Ag), then experimentally confirmed that the predicted (Cu, Ag) co‐doped CeO2 showed higher activity than pure CeO2 and other TM‐doped CeO2. This was attributed to the easy formation of oxygen vacancies in the lattice of CeO2. Our study demonstrates that the use of a rational design of CeO2‐based catalyst through theoretical calculations and experimental validation can effectively improve the low‐temperature catalytic activity of CO oxidation. Finding the CEO of CeO2: Transition metal (TM) co‐doped CeO2 catalyst for CO oxidation reaction was rationally designed by exploiting the relationship between DFT‐calculated oxygen vacancy formation energy and catalytic activity. Among the 91 binary combinations for co‐doping, DFT calculations predicted that (Cu, Ag) co‐doped CeO2 would have the best catalytic activity for CO oxidation. The following experiments successfully proved that the (Cu, Ag) co‐doped CeO2 indeed had higher activity than pure CeO2 and other TM‐doped CeO2.