Although studies have focused on identifying the association between family-related factors (e.g., family relationship quality) and youth's career decision-making self-efficacy, additional empirical evidence is necessary to clarify the potential factors influencing the connection between family relationship quality and youth's career decision-making self-efficacy. The present study aimed to investigate the impact of youth's perceived levels of family relationship quality on their career decision-making self-efficacy and the mediating role of their positive decision-making skills among 425 youth participants in a southeastern region of the United States. The authors of this study conducted a mediation analysis using longitudinal data at two different time points in order to investigate the mediating effect of youth's positive decision-making skills. Results indicated that family relationship quality did not have a direct association with youth's career decision-making self-efficacy. Instead, youth's positive decision-making skills had a full mediating effect on the association between the quality of youth-family member relationships and their self-efficacy for career decision-making. Implications for family life educators, researchers of youth career development, and family counselors are discussed.