The manipulation of oxygen vacancies (OVs) in metal oxides has progressively emerged as a versatile strategy for improving their catalytic performance. In this study, we aim to enhance the oxygen evolution reaction (OER) performance of cerium oxide (CeO₂) by doping heteroatoms (Fe, Co, Ni) to generate additional OVs. We systematically analyzed both the morphology and electronic structure of the obtained CeO₂ catalysts. The experimental results revealed the self-assembly of two-dimensional (2D) CeO₂ nanosheets, with an approximate thickness of ∼1.7 nm, into 2D nanosheet assemblies (NSAs). Moreover, the incorporation of heteroatoms into the CeO₂ matrix promoted the formation of OVs, resulting in a significant enhancement of the OER performance of CeO₂. Among them, the Co-doped CeO₂ NSAs sample displayed the highest activity and durability, with almost negligible activity loss during extended operating periods. The roles of heteroatom doping in improving OER activity were explored by DFT calculations. The produced OVs improve the adsorption of hydroxyl groups (OH⁻), promote the deprotonation process, and increase more active sites. These findings suggest that doping CeO₂ with heteroatoms is a promising strategy for improving electrocatalytic OER activity, with great potential for the development of clean energy technologies, including but not limited to water splitting and fuel cells.