Harmful algal bloom events can result from the rapid growth, or bloom, of photosynthesizing organisms in natural bodies of fresh, brackish, and salt water. These events can be exacerbated by nutrient pollution (e.g., phosphorus) and warming waters and other climate change effects (1); have a negative impact on the health of humans, animals, and the environment; and damage local economies (2,3). U.S. harmful algal bloom events of public health concern are centered on a subset of phytoplankton: diatoms, dinoflagellates, and cyanobacteria (also called blue-green algae). CDC launched the One Health Harmful Algal Bloom System (OHHABS) in 2016 to inform efforts to prevent human and animal illnesses associated with harmful algal bloom events. A total of 18 states reported 421 harmful algal bloom events, 389 cases of human illness, and 413 cases of animal illness that occurred during 2016-2018. The majority of harmful algal bloom events occurred during May-October (413; 98%) and in freshwater bodies (377; 90%). Human and animal illnesses primarily occurred during June-September (378; 98%) and May-September (410; 100%). Gastrointestinal or generalized illness signs or symptoms were the most frequently reported (>40% of human cases and >50% of animal cases); however, multiple other signs and symptoms were reported. Surveillance data from harmful algal bloom events, exposures, and health effects provide a systematic description of these occurrences and can be used to inform control and prevention of harmful algal bloom-associated illnesses.