Objectives This study examines the effectiveness of a multidisciplinary intervention for African American grandmothers raising grandchildren on the relationship between dichotomized levels of mental health stress (low vs. high) and elevated levels of psychological distress, mediated by perceptions of family resources. Method A nonrandom sample of African American grandmothers (N = 679) was assessed to test the predictive relations among study constructs in the context of a prospective mediational model. Results Perception of family resources contributes to lower psychological distress among custodial grandmothers exhibiting low and high levels of mental health stress. There was no significant difference in the strength of the mediated effects between the 2 mental health stress groups. Conclusion The findings suggest appropriate resource‐focused interventions can enhance grandmothers’ subjective assessments of family resources and reduce psychological distress. However, additional research is needed to ascertain the consistency and generalizability of findings.