Eastern equine encephalitis virus (EEEV) is a mosquito-borne alphavirus found in the eastern United States. Eastern equine encephalitis virus disease in humans is rare but can result in severe, often fatal, illness. This report summarizes the national EEEV surveillance data for 2003 through 2016, including human disease cases and nonhuman infections. Over the 14-year period, 633 counties from 33 states reported EEEV activity; 88% of those counties reported EEEV activity only in nonhuman species. A total of 121 human cases of EEEV disease were reported, with a median of eight cases reported annually. The national average annual incidence of EEEV neuroinvasive disease was 0.03 cases per million population. States with the highest average annual incidence included New Hampshire, Massachusetts, Vermont, Maine, and Alabama. Eastern equine encephalitis virus neuroinvasive disease incidence was highest among males and among persons aged < 5 and > 60 years. Overall, 118 (98%) case patients were hospitalized and 50 (41%) died. The case fatality ratio was highest among case patients aged ≥ 70 years. Nonhuman surveillance data indicate that the geographic range of EEEV is much greater than human cases alone might suggest. In areas where the virus circulates, health-care providers should consider EEEV infection in the differential diagnosis for meningitis and encephalitis. Providers are encouraged to report suspected cases to their public health department to facilitate diagnosis and consider interventions to mitigate the risk of further transmission. Because human vaccines against EEEV are not available, prevention depends on community efforts to reduce mosquito populations and personal protective measures to decrease exposure to mosquitoes.