SARS-CoV-2 is frequently transmitted by aerosol, and the sterilization of the virus in airflows has numerous potential applications. We evaluated a UV-C illuminator similar to what might be incorporated into tubing of a mechanical ventilator for its ability to block transmission of the airborne virus from infected to naïve hamsters. Hamsters protected by the UV system were consistently protected from infection, whereas non-protected hamsters uniformly became infected and displayed virus shedding and high burdens of virus in respiratory tissues. The efficiency and speed with which the virus in flowing air was inactivated using this system suggests several applications for mitigating transmission of this virus.