To study the performance of the main windshield of a commercial aircraft that has been verified to be airworthy by bird-strike tests against unmanned aerial vehicle (UAV) impact at high-speed, a typical light UAV with various possible flight postures and the main windshield of a commercial aircraft are considered. The transient impact responses at critical moments, energy change and contact force of a multi-layer windshield impacted by a UAV with different postures are investigated using a simulation method based on the models verified by the high-speed impact test between the whole UAV and the full-size nose. This study shows that the flight posture of the UAV has a significant effect on the damage to the windshield. When the abdomen of a typical light UAV maintains a posture parallel to the plane of the windshield, the high-speed impact would cause catastrophic damage to the windshield and no longer be airworthy. Simultaneously, the damage to the aircraft windshield caused by UAV collision is far more serious than that caused by bird strikes under similar collision conditions. The mass-concentrated components of the UAV and their high-hardness characteristics are the main factors of affecting multi-layer glass of windshield damage. The degree of damage to the windshield is positively related to the absorbed energy rather than the impact contact force. In this study, the impact simulation results between the windshield and UAV with different flight postures are verified qualitatively by testing, which provides a rational understanding and technical pre-research support for emerging and increasingly frequent potential safety hazards in air transport practice.