People who consume tobacco are at greater risk of developing severe COVID-19. Unfortunately, the COVID-19 pandemic reduced the accessibility of tobacco cessation services as a result of necessary social restrictions. Innovations were urgently needed to support tobacco cessation during the pandemic. Virtual humans are artificially intelligent computer agents with a realistic, humanlike appearance. Virtual humans could be a scalable and engaging way to deliver tobacco cessation information and support. Florence, a virtual human health worker, was developed in collaboration with the World Health Organization to remotely support people toward tobacco cessation during the COVID-19 pandemic. Florence delivers evidence-based information, assists with making quit plans, and directs people to World Health Organization–recommended cessation services in their country. In this viewpoint, we describe the process of developing Florence. The development was influenced by a formative evaluation of data from 115 early users of Florence from 49 countries. In general, Florence was positively perceived; however, changes were requested to aspects of her design and content. In addition, areas for new content were identified (eg, for nonsmoker support persons). Virtual health workers could expand the reach of evidence-based tobacco cessation information and personalized support. However, as they are a new innovation in tobacco cessation, their efficacy, feasibility, and acceptability in this application needs to be evaluated, including in diverse populations.