Racial and sexuality-based discrimination can induce depressive symptoms among Black sexual minority men and transgender women (BSMM/BTW). BSMM and BTW who disclose their sexuality to parents may be better prepared to cope with discrimination. We explored the relationship between discrimination and depression among BSMM and BTW and whether parental disclosure modified this relationship. Secondary analysis of The MARI Study was used to test the relationship between discrimination and depression modified by level of disclosure of sexuality to parents among 580 BSMM and BTW in Jackson, Mississippi, and Atlanta, Georgia. Bivariate tests and linear regression models were stratified by sexuality disclosure to parents. Discrimination was associated with greater depression, with significant dose-response modification across levels of disclosure. After adjustment, maximum discrimination scores were associated with depression scores 10.7 units higher among participants with very open disclosure (95% CI, 10.4-11.8), 15.3 units higher among participants with somewhat open disclosure (95% CI, 3.7-26.9), and 19.5 units higher among participants with no disclosure (95% CI, 10.2-26.8). Disclosure of sexuality to supportive parents can substantially benefit the mental health of BSMM and BTW. Future studies should explore intervention approaches to providing social support for BSMM and BTW in unsupportive families.