Work design research typically views employee work characteristics as being primarily determined by the work environment and has thus paid less attention to the possibility that the person may also influence employee work characteristics and in turn accounts for the work characteristics–well‐being relationships through selection. Challenging this conventional view, we investigated the role of a fundamental individual difference variable—people's genetic makeup—in affecting work characteristics (i.e., job demands, job control, social support at work, and job complexity) and in explaining why work characteristics relate to subjective and physical well‐being. Our findings based on a national US twin sample show sizable genetic influences on job demands, job control, and job complexity, but not on social support at work. Such genetic influences were partly attributed to genetic factors associated with core self‐evaluations. Both genetic and environmental influences accounted for the relationships between work characteristics and well‐being, but to varying degrees. The results underscore the importance of the person, in addition to the work environment, in influencing employee work characteristics and explaining the underlying nature of the relationships between employee work characteristics and their well‐being. Copyright © 2016 John Wiley & Sons, Ltd.