Water-gas shift (WGS) reaction is an important process for industrial hydrogen production. The side reaction of methanation often causes unavoidable loss of H-2 along with this reaction. Here, we report a Rh-1/TiO2 single-atom catalyst (SAC) with appreciable loading of 0.37 wt %, which exhibited an overall CO conversion of approximate to 95% but without any methanation at 300 degrees C, even under CO2- and H-2-rich WGS stream. The specific activity of this SAC was around four times higher than that of cluster catalyst, which meanwhile suffered from unfavorable methanation. It was found that Rh single atoms promoted the formation of more oxygen vacancies on the TiO2 support to activate H2O to generate H-2 and prohibited the dissociation of H-2 compared with Rh clusters, leading to the enhanced activity and selectivity for WGS. (c) 2016 American Institute of Chemical Engineers AIChE J, 63: 2081-2088, 2017