Although American Indian and Alaska Native people make up less than 2% of the US population, they are disproportionally affected by adverse health outcomes, including disabilities. The Indigenous community of the Mohawk Nation at Akwesasne has faced significant environmental contamination since the 1970s, resulting from operations of three aluminum foundries near the community. The aim of this study was to explore the potentially moderating effects of social support and cultural identity on disability, taking into account age, sex, and health comorbidities among 119 Akwesasne Mohawk adults. We used the World Health Organization Disability Assessment Schedule II (WHO-DAS II) to measure disability, the Duke University Social Support Scale with Likert-type responses to quantify social support, and the Orthogonal Ethnic Identification Scale to calculate cultural affiliation. We found that overall social support was significantly negatively associated with disability related to self-care (Relative Risk (RR) = 0.96, 95% Confidence Interval (CI): 0.93, 1.00). Both family support (RR = 0.97, 95% CI: 0.94, 0.99) and non-family support (RR = 0.97, 95% CI: 0.94, 1.00) were negatively associated with disabilities that prevent full participation in society. Cultural affiliation to either the white culture or the Mohawk culture was not significantly associated with disability. Although preliminary, our findings may help inform clinicians advising American Indians and Alaska Natives with disabilities on helpful interventions to provide greater social support. This may in turn improve the quality of life of indigenous communities facing a high prevalence of disability.