Adverse childhood experiences (ACEs) can result in trauma that persists into adulthood. The goal of this study was to estimate the associations of ACEs with health-related quality of life (HRQOL) metrics in American Indian and Alaska Native (AI/AN) adults in the United States using data from the 2015-2019 Behavioral Risk Factor Surveillance System. Adults (n = 1,389) were asked about current health and ACEs during childhood. ACE score was defined as the total number of ACEs reported. HRQOL outcomes included fair or poor general health, poor general health, poor physical health, poor mental health, and poor physical or mental health. Weighted logistic regression was used to measure the association between ACE score and HRQOL outcomes. A unit increase in ACE score was associated with 14% greater odds of fair or poor general health (OR = 1.14, 95% CI: 1.06, 1.23) and nearly 30% greater odds of poor mental health in the last 30 days (OR = 1.29, 95% CI: 1.20, 1.40). ACEs pose a threat to quality of life in AI/AN adults. These results highlight the need for ACEs prevention in AI/AN communities. Future studies should identify factors associated with resilience to best inform prevention and treatment strategies.