Chemical looping partial oxidation of methane to syngas is a promising process. Thermodynamic and kinetic analysis both forecast the NiO/Ce2(SO4)3–MgO is a prospective oxygen carrier (OC) to this process, which enables with 100% syngas selectivity, 2.15H2/CO ratio, excellent methane conversion and stable cycling characteristic. Compared with Ce2(SO4)3, the methane conversion rate rise by 73.19% because of the excellent lattice oxygen availability, less carbon deposit, and large specific surface area. The distinctive pore structure also provides a favorable reaction environment. Through the density functional theory, Ni doping can lower the energy barrier (Eb), promote lattice oxygen activation and diffusion, and the oxygen vacancy (Ov) can further promote these processes. CH3 → CH2 + H (TS2) is the rate-limiting step. Compared with Ce2(SO4)3, the Ni doping can reduce Eb by 16.8%, and the Ov can further reduce it by 43.0%. It does not change when the Ov concentration is more than 1.96%.