Couple-based HIV interventions that increase uptake of two or more effective biomedical HIV prevention methods may be a promising HIV prevention strategy for young Black and Latino heterosexual couples. We conducted in-depth, semi-structured individual interviews with 23 Black and Latino adolescent and young adult heterosexual couples that explored their attitudes toward using combination HIV prevention methods (CHPMs). A qualitative hybrid thematic analysis approach was used to identify key themes. Themes included: (a) attitudes that encouraged uptake—CHPMs increased assurance of safety against HIV/sexually transmitted infections and (b) attitudes that impeded uptake—CHPMs are too much to do and are not appropriate for serious relationships. Although Black and Latino adolescents and young adults may recognize the combined protective benefits of using multiple HIV prevention methods, personal and relational considerations play an instrumental role in uptake of CHPMs.