Objective: Perceived discrimination poses risks for psychological distress among Asian Americans, but the differential impact of general unfair treatment and racial discrimination has not been examined. Although social support from distal sources reduces discrimination-related distress either directly or as a buffer, the unique roles of spousal support have remained understudied. Nativity status was examined as another moderator of these relationships to resolve previous inconsistent findings regarding its relationship to the discrimination-distress link. Method: Data were from 1,626 U.S.- and foreign-born Asian American adults (M-age = 42.17 years; n = 1,142 married/cohabiting) in the nationally representative National Latino and Asian American Study, who reported on experiences of unfair treatment, racial discrimination, social supports from spouses, family, friends, and neighborhood, and psychological distress. Results: Hierarchical multiple regressions showed that both unfair treatment and racial discrimination predicted psychological distress, and spousal support predicted distress above and beyond distal forms of social support in the context of perceived discrimination. Moderation analyses revealed that spousal support buffered against negative psychological consequences of unfair treatment, but not racial discrimination. Spousal support was not differentially protective as a function of nativity; however, U.S.-born respondents reacted with greater distress to unfair treatment than their foreign-born counterparts. Conclusions: Psychological effects of both general and race-based discrimination, and the unique contributions of distinct sources of social support, are important to understanding adjustment and cultural transition among Asian Americans. Nativity differentially influences effects of unfair treatment. Implications for future research are discussed.