Purpose: Multigenerational families are becoming increasingly common in the U.S. This trend is primarily driven by three-generation households with grandparents. The coresident grandparents play an important role in adolescents’ health and well-being. Thus, by focusing on three-generational households, this study examined the determinants of living in three-generational households among adolescents within the contexts of the social–economic, cultural, and family factors that influence grandparent co-residence by ethnic groups. Methods: This study used the National Longitudinal Study of Adolescent to Adult Health (Wave I–III). The study sample included 10,093 adolescents, including White, African American, Asian, and Hispanic youth. This study conducted a series of logistic regression models to examine the associations between co-residence with grandparents and significant predictors in family structure, socioeconomic status, and cultural factors for youths in the U.S. by ethnic groups. Results: For White families, lower socioeconomic status was more pertinent to three-generational co-residence. However, the associations were in the opposite direction for Hispanic and African American households, indicating that higher socioeconomic status families were found to live with grandparents in those groups. For Hispanic families, adolescents from Spanish-speaking homes were more likely to live in three-generational households than those from English-speaking homes. Implications: These results suggest that family characteristics in three-generational households vary by ethnic group. Notably, family cultural factors were significant determinants of co-residence with grandparents in three-generational households, especially in Hispanic families. This study contributes to the sustainability discourse by examining the intersectionality of cultural maintenance, health and well-being, and aging society among three-generational households in the United States.