Objective: In this work, we aimed to develop a practical, structured approach to identify narratives in public online conversations on social media platforms where concerns or confusion exist or where narratives are gaining traction, thus providing actionable data to help the WHO prioritize its response efforts to address the COVID-19 infodemic. Methods: We developed a taxonomy to filter global public conversations in English and French related to COVID-19 on social media into 5 categories with 35 subcategories. The taxonomy and its implementation were validated for retrieval precision and recall, and they were reviewed and adapted as language about the pandemic in online conversations changed over time. The aggregated data for each subcategory were analyzed on a weekly basis by volume, velocity, and presence of questions to detect signals of information voids with potential for confusion or where mis- or disinformation may thrive. A human analyst reviewed and identified potential information voids and sources of confusion, and quantitative data were used to provide insights on emerging narratives, influencers, and public reactions to COVID-19–related topics. Results: A COVID-19 public health social listening taxonomy was developed, validated, and applied to filter relevant content for more focused analysis. A weekly analysis of public online conversations since March 23, 2020, enabled quantification of shifting interests in public health–related topics concerning the pandemic, and the analysis demonstrated recurring voids of verified health information. This approach therefore focuses on the detection of infodemic signals to generate actionable insights to rapidly inform decision-making for a more targeted and adaptive response, including risk communication.