Considering that aircrafts are typical targets for laser weapons, and aircraft materials are used under complex mechanical conditions, the response of these materials under laser and prestressing holds significant value in the aeronautic industry. However, current research on material response under combined laser and prestressing mainly focuses on mechanical failure affected by laser irradiation, with limited in-depth understanding of laser ablation characteristics and microscopic mechanisms. In this study, we investigate the laser ablation characteristics of LY12-CZ alloy by means of experiment and simulation. We analyze the ablative morphology under prestressing and characterize microstructure and element distribution in the remaining samples. The Vickers hardness test along the radial direction of the heat source is carried out. In addition, a finite element simulation of laser ablation under prestressing is performed based on the fully coupled thermal-stress analysis method. The experimental findings reveal three distinct structures along the radial direction of the spot: the dendrite structure near the spot, the equiaxed grain structure in the middle, and the original structure far away from the spot. Both the dendrite and equiaxed grain structures exhibit severe segregation of Cu element, while the equiaxed grain structure also experiences high internal stress. The hardness in the dendrite structure is close to 80 HV and increases sharply to around 120 HV in the equiaxed grain structure. In the transition zone from the equiaxed grain structure to the original structure, the hardness decreases first and then increases. Prestressing does not have an obvious effect on the distribution of microstructure, element segregation, and hardness after laser ablation. Simulation results indicate that the temperature field is not significantly influenced by the applied prestress. The thermal stress caused by the rise in irradiation temperature is much higher than the applied prestress, leading to the formation of burn-through cavities and local thermal softening of the material. It is found that prestressing does not significantly alter the laser ablation characteristics of LY12-CZ alloy.