The Fischer-Tropsch synthesis (FTS) has been studied for decades; however, it is very difficult to simultaneously obtain a high one-pass CO conversion and a high selectivity of long-chain (C5+) hydrocarbons. A layered CoMn/TiO2 catalyst is fabricated and used as an efficient catalyst in FTS. The unique layered structure of the CoMn/TiO2 catalyst effectively inhibits the agglomeration of Co nanoparticles and enhances the diffusion of the reactants and products in FTS. The catalyst exhibits superior activity, high C5+ selectivity, and excellent stability due to its unique multiple mesopores structure as well as high cobalt dispersion. Even at a nearly complete one-pass CO conversion (>95%), which is considered to be a very harsh condition in the FTS reaction, CoMn/TiO2 still exhibits a high C5+ hydrocarbon selectivity of around 93% and a very low selectivity of undesired Cl products (CH4 and CO2) of below 4.5%.