The electrochemical CO2 reduction reaction (CO2RR) is a promising pathway for converting CO2 into valuable products such as carbon monoxide (CO). Here we show that a remarkably high CO selectivity can be achieved in a gas diffusion electrode-based CO2RR flow cell by using different characteristics of the proton and CO2 reduction reactions over a wide range of pHs, while H2 evolution from H2O reduction can be effectively avoided. The potential window of a high-performance Ni single-atom catalyst for CO2RR does not overlap with that for H2O reduction; this allows CO selectivity to exceed 90% in a pH 2 electrolyte, thereby attaining a CO2-to-CO conversion rate of approximately 77%. Effects of electrolyte compositions on CO2RR are also evaluated. Technoeconomic and life cycle assessments establish that CO2RR is more favorable in acidic conditions, which can minimize the additional CO2 recycling and electrolyte regeneration processes, if surplus or cheap renewable electricity is available.