Despite efforts to reduce health disparities, many American Indian and Alaska Native (AI/AN) populations, including older adults, experience elevated levels of depression and associated suicide. Although adverse childhood experiences (ACEs) 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 479 AI and Caucasian respondents over the age of 50. The survey included standardized measures such as the Geriatric Depression Scale-Short Form, ACE Questionnaire, and Multidimensional Scale of Perceived Social Support. Hierarchical multivariate regression analyses were conducted to evaluate the main hypotheses of the study. Results indicate that two dimensions of ACEs (childhood neglect and 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 of depressive symptoms. ACEs may play a significant role in depression among AI/AN populations across the life course and into old age. Social support offers a promising mechanism to bolster resilience among AI/AN older adults.