Despite efforts to promote health equity, many American Indian and Alaska Native (AI/AN) populations, including older adults, experience elevated levels of depression. Although adverse childhood experiences (ACE) and social support are well-documented risk and protective factors for depression in the general population, little is known about AI/AN populations, especially older adults. The purpose of this study was to examine factors related to depression among a sample of AI older adults in the midwest. Data were collected using a self-administered survey completed by 233 AIs over the age of 50. The survey included standardized measures such as the Geriatric Depression Scale-Short Form, ACE Questionnaire, and the Multidimensional Scale of Perceived Social Support. Hierarchical multivariate regression analyses were conducted to evaluate the main hypotheses of the study. Results: Two dimensions of ACE (i.e., childhood neglect, household dysfunction) were positively associated with depressive symptoms; social support was negatively associated with depressive symptoms. Perceived health and living alone were also significant predictors. ACE may play a significant role in depression among AI/AN across the life course and into old age. Social support offers a promising mechanism to bolster resilience among AI/AN older adults.