In this study, a pulsed laser operating at a wavelength of 1064 nm and with a pulse width of 100 ns was utilized for the removal of paint from the surface of a 2024 aluminum alloy. The experimental investigation was conducted to analyze the influence of laser parameters on the efficacy of paint layer removal from the aircraft skin’s surface and the subsequent evolution in the microstructure of the laser-treated aluminum alloy substrate. The mechanism underlying laser cleaning was explored through simulation. The findings revealed that power density and scanning speed significantly affected the quality of cleaning. Notably, there were discernible damage thresholds and optimal cleaning parameters in repetitive frequency, with a power density of 178.25 MW/cm2, scanning speed of 500 mm/s, and repetitive frequency of 40 kHz identified as the primary optimal settings for achieving the desired cleaning effect. Thermal ablation and thermal vibration were identified as the principal mechanisms of cleaning. Moreover, laser processing induced surface dislocations and concentrated stress, accompanied by grain refinement, on the aluminum substrate.