Prior research finds internalized homonegativity to be associated with reduced relationship quality in same-sex relationships. Yet, few studies on internalized homonegativity have examined different dimensions of relationship quality, the mechanisms involved, or whether the association varies by gender. This study sought to better understand the link between internalized homonegativity and relationship quality by examining multiple aspects of relationship quality, the mediational roles of anxiety and depressive symptoms, and the moderating role of gender. Using data from an online survey, we conducted analyses with a sample of 99 men and 86 women who were living in the United States, at least 18 years old, and in a same-sex relationship for at least 3 months. In the full analytic sample with both men and women, bootstrap mediation analyses revealed that internalized homonegativity was directly associated with greater anxiety and depressive symptoms, as well as indirectly associated with less relationship satisfaction and intimacy through the mechanism of greater depressive symptoms. Subsequent moderated mediation analyses revealed that internalized homonegativity’s direct associations with greater anxiety and depressive symptoms as well as indirect associations with less relationship satisfaction, commitment, and intimacy through greater depressive symptoms were significant for men but not for women. A better understanding of these dynamics can guide future research, inform clinical practice, and improve individual and relational functioning for individuals in same-sex relationships.