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Fifteen cities across the world have been selected to investigate the public health co-benefits of PM_2.5 reduction, during a period when various non-pharmaceutical interventions (NPIs) were adopted in the COVID-19 pandemic. Through applying a public health model, AirQ+, substantial spatial variations of global public health co-benefits were identified. Differences in seasonal air quality and population baselines were key underlying factors. For cities in North America, NPIs were introduced during the low pollution season, generating no co-benefits. On the other hand, tremendous health co-benefits were observed for cities in India and China, due to the high PM_2.5 background with a large population. Among all, New Delhi has received the largest co-benefits, which saved over 14,700 premature deaths. As the pollution level (i.e., 45 μg m⁻³) with NPIs still exceeded the air quality standard, more rigorous emission controls are urgently needed to protect the public′s health in India. At last, a novel and practical tool for co-benefit screening was developed using data from one of the global measurement networks (i.e., IQAir).