The South Asian (SA) population has been underrepresented in research linking discrimination with health indicators; studies that focus on the unique cultural and psychosocial experiences of different SA subgroups are needed. The purpose of this study was to examine associations between self-reported discrimination and mental health among Asian Indians (AIs), and whether traditional cultural beliefs (believing that SA cultural traditions should be practiced in the United States), coping style, and social support moderated these relationships. AIs (N = 733) recruited from community-based sampling frames for the Mediators of Atherosclerosis in South Asians Living in America study were included in this analysis. Multiple linear regression analyses were employed to evaluate relationships between discrimination and depressive symptoms, anger, and anxiety. Participants (men = 54%) were on average 55 years of age and had high levels of English proficiency, education, and income. Higher reports of discrimination were significantly associated with higher depressive symptoms, B = .27 (.05) p < .001, anger, B = .08 (.01), p < .001, and anxiety, B = .10 (.01), p < .001. Associations between discrimination and anger, B = −.005 (.002), p = .02, were weakest among those with stronger cultural beliefs. The link between discrimination and anxiety was attenuated by an active coping style, B = −.05 (.03), p = .04. In sum, self-reported discrimination appeared to adversely impact the mental health of AIs. Discrimination may be better coped with by having strong traditional cultural beliefs and actively managing experiences of discrimination.