Asian Americans have been identified as a racial group that is disproportionately affected by childhood trauma. The goal of this study was to assess if religion/spirituality moderate the effects of childhood trauma on adult depressive symptoms among a sample of South Asians in the USA. Our analysis drew from the study on stress, spirituality, and health (SSSH) questionnaire fielded in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study (n = 990) during 2016-2018. A series of regression models with multiplicative interaction terms were conducted. Emotional neglect, emotional abuse, and physical neglect were associated with higher depressive symptoms. Higher religious attendance and negative religious coping techniques were found to exacerbate this relationship. There were two findings conditional on gender. Among men, gratitude and positive religious coping also exacerbated the relationship between childhood trauma and depressive symptoms. Negative religious coping also exacerbated the association between childhood trauma and depressive symptoms for women. This is the first community-based study of US South Asians to consider the association between various forms of childhood trauma and depressive symptom outcomes. South Asians remain an understudied group in the religion and health literature, and this study sheds light on the important differences in the function and effectiveness of religion/spirituality for those faced with early life trauma.