Confronted with a novel coronavirus, countries worldwide were forced to rapidly adjust their public health systems, platforms, and tools to respond to COVID-19. The US Centers for Disease Control and Prevention (CDC) and its global partners adapted health systems and programs originally developed for other purposes, such as controlling the HIV/AIDS pandemic through the US President’s Emergency Plan for AIDS Relief (PEPFAR), Global Health Security Agenda implementation, influenza surveillance, and vaccine-preventable disease elimination and eradication. This special supplement of Emerging Infectious Diseases highlights responses to the early phases of the COVID-19 pandemic from >80 countries, spanning 6 continents and representing >130 organizations. This article summarizes global adaptations of core public health functions during COVID-19: surveillance, information, and laboratory systems; workforce, institutional, and public health capacity; and clinical and health services delivery.