There is a lack of studies examining sexually transmitted disease (STD) diagnosis among subgroups of Black/African American population. We examined the association between STD diagnosis and sociodemographic, sexual identity, mental health, and substance use disorder factors based on sex among Black/African American adult population (N = 15,924). Secondary data analysis was computed using the 2017 to 2019 National Survey on Drug Use and Health, a cross-sectional survey. The prevalence of STDs was higher among Black/African American females (3.01%) than among males (2.61%). Compared to heterosexual females, bisexual females were more likely to have STDs. Males who identified as gay or bisexual were more likely than heterosexual individuals to have STDs. Males or females who experienced marijuana use disorder were more likely than their counterparts to be diagnosed with STDs. Major depressive episode (MDE), alcohol use disorder (AUD), opioid use disorder (OUD), marijuana use disorder, and illicit drugs other than marijuana moderated the association between STD diagnosis and sexual identity based on sex. This study revealed differences in STD diagnosis based on the intersection of sex and sexual identity, mental health, and substance use among Black/African American adults for tailored intervention development efforts.