The literature on personality trait development has mainly focused on influences of life experiences in one single life domain (e.g., work or family) separate from one another and has primarily examined personality development in early life stages. Thus, less attention has been devoted to influences from interplays across different life domains and personality development in middle and late adulthood. Synthesizing the literature on personality science and organizational research, we built a theoretical model and investigated what, how, and why the interplay between two central life domains—work and family—may be related to personality trait development of people at their middle and late life stages, and more important, change-related reciprocal relationships between personality traits and work–family experiences. Generally, convergent findings with data from two longitudinal studies (National Survey of Midlife in the United States, maximum N = 3,192, three waves; and Health and Retirement Study, maximum N = 1,133, three waves except anxiety) revealed that work-to-family conflict, family-to-work conflict, work-to-family facilitation, and family-to-work facilitation mostly had lagged effects on changes of Conscientiousness, Extraversion, and Neuroticism, and the influences were generally channeled through changes of anxiety. Personality traits also had lagged influences on changes of work–family experiences, with some influences deteriorating over time. Change-related reciprocal relationships were recorded mainly between Neuroticism and Extraversion with work–family experiences. Some selection effects were larger than socialization effects. Our research contributes to the personality and the work–family literature and represents a useful example of cross-fertilization of research in different areas of psychology to advance personality research.