To investigate the epidemiology of ocular exposures reported to poison control centers in the United States. A retrospective analysis of ocular exposures from 2000 to 2016 was conducted using National Poison Data System data. United States poison control centers received 1,436,683 reports of ocular exposures during 2000-2016, averaging 7,043 exposures per month. The annual frequency of ocular exposures declined significantly by 37.2% from 2006 to 2016. The ocular exposure rate per 10,000 US residents was highest among children < 6 years of age (10.7), particularly among 2-year-olds (20.5), and was lowest among adults ≥ 20 years of age (1.9). The majority of the exposures resulted in minor effects (51.4%). Among exposed individuals, 23.0% were treated and released and 0.3% were admitted to a healthcare facility. Household cleaning products (22.2%), cosmetics/personal care products (15.7%), and pesticides (7.4%) were the most common substance categories associated with exposures, but exposures to building and construction products (18.1%), industrial cleaners (14.9%), and chemicals (14.1%) resulted in a higher percentage of moderate or major effects. In addition, exposures to alkaline substances had a higher percentage of moderate or major effects. Although the annual frequency of ocular exposures declined during the last decade, the number of exposures remains high, particularly among young children. The commonly associated substance categories identified in this study represent important preventable sources of morbidity.