SUMMARY The Earth's subsurface structure provides critical insights into sustainable resource management and geologic evolution. The airborne electromagnetic (AEM) method is an efficient data acquisition technique and can be used to image the underground resistivity structure with high spatial resolution. However, inversion of the increasingly huge volume of AEM data poses a heavy computational burden. In this study, we develop a hybrid deep learning-based approach by using the physics-guided neural network (PGNN) which incorporates the governing physical laws into the loss function to solve the AEM inverse problem. The PGNN integrates the strength of data-driven method for representation learning with electromagnetic laws and allows for the underlying physical constraints to be strictly satisfied. We validate the effectiveness of our approach using both synthetic and field datasets. Compared with the classic Gauss–Newton method, our PGNN inversion system shows strong robustness against multiple noise sources and reduces the risk of being trapped in local extrema. Moreover, the PGNN-inverted results are physically more consistent with the AEM observations compared to the purely data-driven approach. Application to the field AEM data from Northern Australia demonstrates that the PGNN-based inversion framework effectively estimates the subsurface electrical properties with considerable lateral continuity and significantly higher efficiency, completing the inversion of more than 2734000 AEM soundings taking only minutes on a common PC. Our proposed PGNN-based method shows great promise for large-scale underground resistivity imaging, and the well-identified subsurface resistivity structure can effectively improve our understanding of resource distributions and geological hazards.