Objectives: Health literacy is often viewed as an essential skill set for successfully seeking health information to make health-related decisions. However, this general understanding has yet to be established with the use of nationally representative data. The objective of this study was to provide the first nationally representative empirical evidence that links health information seeking behaviors with health literacy among middle-age to older adults in the United States. Methods: Data were obtained from the 2012/2014 Program for the International Assessment of Adult Literacy (PIAAC). Our analytic sample is representative of adults age 45 to 74 years (N = 2,989). Results: Distinct components of health literacy (i.e., literacy and numeracy) were uniquely associated with the use of different health information sources (e.g., health professionals, the Internet, television). Discussion: Findings should be useful for government agencies and health care providers interested in targeting health communications, as well as researchers who focus on health disparities.