For more than 30 years, the network of Centers for Disease Control and Prevention (CDC)-funded Prevention Research Centers (PRCs) has worked with local communities and partners to implement and evaluate public health interventions and policies for the prevention of disease and promotion of health. The COVID-19 pandemic tested the PRC network's ability to rapidly respond to multiple, simultaneous public health crises. On April 28, 2020, to assess the network's engagement with activities undertaken in response to the early phase of the pandemic, PRC network leadership distributed an online survey to the directors of 34 currently or formerly funded PRCs, asking them to report their PRCs' engagement with predetermined activities across 9 topical areas and provide case studies exemplifying that engagement. We received responses from 24 PRCs, all of which reported engagement with at least 1 of the 9 topical areas (mean, 5). The topical areas with which the greatest number of PRCs reported engagement were support of frontline agencies (21 of 24, 88%) and support of activities related to health care (21 of 24, 88%). The mean number of activities with which PRCs reported engagement was 11. The PRCs provided more than 90 case studies exemplifying their work. The results of the survey indicated that the PRCs mobilized their personnel and resources to support the COVID-19 response in less than 6 weeks. We posit that the speed of this response was due, in part, to the broad and diverse expertise of PRC personnel and long-standing partnerships between PRCs and the communities in which they work.