Nitrogen dioxide (NO2) sensors experience the drawback of requiring high operating temperatures because of the low charge transfer ability of gas-sensing materials. Herein, an advanced NO2 sensor resistant to interference is designed using the interfacial energy barriers of a hierarchical CuO/ZnO composite. With the benefits of abundant desirable defect features, and the amplification effect of heterojunctions, the sensor based on CuO/ZnO composite with 10% Cu(CH3COO)2·H2O (S2) shows outstanding performance in terms of faster response and recovery time (1.8-fold/1.1-fold), higher response (3.1-fold), and lower power consumption (140℃ decrease) compared to the pristine ZnO sensor. Furthermore, the composite sensor exhibits long-term stability and reproducibility, indicating the potential promise of CuO/ZnO heterojunctions in interference-resistant detection of low-concentration NO2 in real applications. This study not only provides a rational solution to designing advanced gas sensors by tuning the interfacial energy barriers of heterojunctions, but also provides a fundamental understanding of CuO structures in the gas-sensing field.