Abstract: A novel multi-layer and multi-physics co-simulation algorithm is proposed for analyzing the effect of high power microwave (HPM) on semiconductors, circuits and electronic systems. This algorithm is based on semiconductors physical model to realize the simulation of semiconductors, and the model is constituted of multi-physic equations, electromagnetic equations, semiconductor physics and thermal equations. A co-simulation method is employed, which incorporates the multi-physics simulation for semiconductors into the equivalent-model based circuit simulation, thus the simulation is extended from semiconductors to circuits. The algorithm achieves the simulation for the HPM effect on electronic systems, by incorporating the multi-physics simulation for circuits with the electromagnetic field simulation. The electronic systems include several circuits, packaging, slot coupling and cable coupling. The principle and procedure of the algorithm is introduced. The proposed algorithm is used to simulate circuits and electronic systems containing commercial P-I-N diodes for various HPM effects, including temperature effect, forward recovery effect and spatial radiation effect in a semi-enclosed cavity. By comparing the simulation results to the measurements, the feasibility and accuracy of the proposed algorithm are validated. Moreover, the proposed algorithm provides clear and intuitive interpretation of the physical mechanism for those HPM effects.