Microwave radiation, as an emerging rock-breaking technology, shows promising applications in assisting mechanical rock fragmentation. To explore the damage mechanisms of microwave radiation on quartz sandstone, this study investigates the variations in uniaxial compressive strength, wave velocity, and macro-microscopic damage characteristics of quartz sandstone under different microwave powers and exposure times. The results indicate that with increasing microwave power and exposure time, the uniaxial compressive strength and elastic modulus exhibit a decreasing trend, while peak strain gradually increases. Both P-wave and S-wave velocities show an overall decline. The damage factor shows an upward trend, and the longer the radiation time, the greater the increase in the damage factor. As microwave power and exposure time increase, the degree of quartz sandstone fragmentation significantly intensifies, resulting in smaller and more numerous fragments. The failure mode shifts from a single shear failure to shear and cleavage along fragile planes. SEM images and fractal dimension (D-value) results indicate that as microwave exposure time increases, the number, length, width, and depth of internal cracks in specimens show an increasing trend, evolving from initial single cracks to superimposed fractures.