The COVID-19 pandemic has caused severe consequences such as long-term disruptions and ripple effects on regional and global supply chains. In this paper, firstly, we design simulation models using AnyLogistix to investigate and predict the pandemic’s short-term and long-term disruptions on a medical mask supply chain. Then, the Green Field Analysis experiments are used to locate the backup facilities and optimize their inventory levels. Finally, risk analysis experiments are carried out to verify the resilience of the redesigned mask supply chain. Our major research findings include the following. First, when the pandemic spreads to the downstream of the supply chain, the duration of the downstream facilities disruption plays a critical role in the supply chain operation and performance. Second, adding backup facilities and optimizing their inventory levels are effective in responding to the pandemic. Overall, this paper provides insights for predicting the impacts of the pandemic on the medical mask supply chain. The results of this study can be used to redesign a medical mask supply chain to be more resilient and flexible.