The COVID-19 pandemic has made it clear that effective public health messaging is an indispensable component of a robust pandemic response system. In this article, we review decades of research from the interdisciplinary field of communication science and provide evidence-based recommendations for COVID-19 public health messaging. We take a principled approach by systematically examining the communication process, focusing on decisions about what to say in a message (i.e., message content) and how to say it (i.e., message executions), and how these decisions impact message persuasiveness. Following a synthesis of each major line of literature, we discuss how science-based principles of message design can be used in COVID-19 public health messaging. Additionally, we identify emerging challenges for public health messaging during the COVID-19 pandemic and discuss possible remedies. We conclude that communication science offers promising public health messaging strategies for combatting COVID-19 and future pandemics.