The US Centers for Disease Control and Prevention, with funding from the US President's Plan for Emergency Relief, implements a virtual model for clinical mentorship, Project Extension for Community Healthcare Outcomes (ECHO), worldwide to connect multidisciplinary teams of healthcare workers (HCWs) with specialists to build capacity to respond to the HIV epidemic. The emergence of and quick evolution of the COVID-19 pandemic created the need and opportunity for the use of the Project ECHO model to help address the knowledge requirements of HCW responding to COVID-19 while maintaining HCW safety through social distancing. We describe the implementation experiences of Project ECHO in 5 Centers for Disease Control and Prevention programs as part of their COVID-19 response, in which existing platforms were used to rapidly disseminate relevant, up-to-date COVID-19-related clinical information to a large, multidisciplinary audience of stakeholders within their healthcare systems.