Abstract The electrochemical N 2 reduction reaction (NRR) offers a promising approach for sustainable NH 3 production, and modulating the structural/electronic configurations of the catalyst materials with optimized electrocatalytic properties is pivotal for achieving high‐efficiency NRR electrocatalysis. Herein, vacancy and heterostructure engineering are rationally integrated to explore O‐vacancy‐rich MoO 3‐ x anchored on Ti 3 C 2 T x ‐MXene (MoO 3‐ x /MXene) as a highly active and selective NRR electrocatalyst, achieving an exceptional NRR activity with an NH 3 yield of 95.8 µg h −1 mg −1 (−0.4 V) and a Faradaic efficiency of 22.3% (−0.3 V). A combination of in situ spectroscopy, molecular dynamics simulations and density functional theory computations is employed to unveil the synergistic effect of O‐vacancies and heterostructures for the NRR, which demonstrates that O‐vacancies on MoO 3‐ x serve as the active sites for N 2 chemisorption and activation, while the MXene substrate can further regulate the O‐vacancy sites to break the scaling relation to effectively stabilize *N 2 /*N 2 H while destabilizing *NH 2 /*NH 3 , resulting in more optimized binding affinity of NRR intermediates toward reduced energy barriers and an enhanced NRR activity for MoO 3‐ x /MXene.