At least one third of U.S. counties experienced extreme or exceptional drought during 2012-2016. This research identified counties that were vulnerable to adverse health effects from extreme and exceptional drought by constructing indices incorporating environmental, population, and community characteristic data. The study identified distinct regions in the west, central, and southeastern U.S. where counties were particularly vulnerable. The majority of vulnerable counties were located in rural areas that may lack the resources to adapt and respond to drought. Interventions to build capacity for drought adaptation and response should be ongoing in the identified vulnerable counties, particularly those in rural areas.