Infectious diseases cause tremendous costs of both human and economy annually. Previously, we have studied the bacterial, fungal, and allergen aerosol inactivation by direct microwave irradiation. Here, we further investigated its effects on airborne viruses. MS2 coliphage used as a human model virus was aerosolized and exposed to the direct microwave irradiation for ~2 min at three different power levels (700, 385, and 119 W). In addition to the survival rate, the viral genes before and after the microwave treatments were also examined using PCR and gel electrophoresis. Direct exposure of airborne MS2 viruses to the microwave irradiation at 700 W for less than 2 min was shown to result in more than 90 % inactivation efficiency, about 65 % at medium power level (385 W), and 50 % at the lowest level (119 W). The aerosol inactivation rate followed a linear relationship with the microwave exposure time (R 2 = 0.9889). Scanning electron images revealed visible damages to the viral surface after the exposure. Damages were also observed to the viral RNA genes coding for coat proteins, among which the A protein gene was completely destroyed. This study demonstrated that even without the filtration the direct microwave irradiation could also achieve rapid inactivation of viral aerosols. The information obtained can provide useful guidance on the development of microwave-based viral threat mitigation solutions in a closed or semi-closed space.