This research uses life course perspective concepts of linked lives and historical time and place to examine the multigenerational effects of relocation experiences on Indigenous families. Data were collected from a longitudinal study currently underway on four American Indian reservations in the Northern Midwest and four Canadian First Nation reserves where residents share a common Indigenous cultural heritage. This article includes information from 507 10- to 12-year-old Indigenous youth and their biological mothers who participated in the study. Results of path analysis revealed significant direct and indirect effects whereby grandparent-generation participation in government relocation programs negatively affects not only grandparent-generation well-being but also ripples out to affect subsequent generations.