Detecting and responding to acute public health threats is one of the World Health Organization's (WHO) most important activities. Therefore, WHO established a unique approach for the global detection and verification of events of potential international public health concern and adopted an all-hazards approach as part of the International Health Regulations (2005), moving beyond a focus on infectious diseases only. Here, we analysed 20-year trends of acute public health events globally. We extracted data on acute public health events reported between 2002 and 2021 from the Event Management System (EMS). EMS is an internal WHO web-based platform used for tracking health threats globally. We examined the designation, source and hazard of events by WHO Region and over time by calculating descriptive statistics and trends using R. Between 2002 and 2021, 7572 events were recorded globally in EMS, ranging from 231 to 576 per year. Of these, 5466 (76%) were designated as substantiated, deemed true acute public health events, and only a small proportion (379, 5%) were unverifiable or had no designation. During the 20-year period, substantiated events were greatest in the WHO African Region (1684 events, 31%) and the WHO Region of the Americas (1312 events, 24%) and, similarly, by year, the burden was highest in those WHO regions. Globally, over time, two-thirds (3536, 65%) of substantiated events were initially reported by WHO and infectious diseases (4298, 79%) were the predominant cause of public health events. However, other causes, including animal origin or zoonoses were also important and disaster related events were on the rise in recent years, particularly in some WHO Regions. WHO has a robust system for global disease detection but health threats are continuously evolving. The impact of climate change and zoonoses is becoming more pronounced, emphasizing the importance of a One Health approach for disease detection.