We examined sexual orientation and sex differences in seven methods of suicide among adult suicides reported in the United States National Violent Death Reporting System (2012–2015; N = 59,075). Overall, most sexual minorities (i.e., lesbians, gay men, bisexuals) identified in the dataset used hanging (38%) followed by firearm (30%) and drug or poison ingestion (20%). Sexual minorities were more likely than heterosexuals to be younger, female, and Black/African American. Multivariate sex-stratified analyses in the overall sample showed that strong sexual orientation differences in lethal methods existed among men but not among women. However, when we compared sex differences in lethal methods among sexual minorities only, we found that lesbian/bisexual women, as compared to gay/bisexual men, were more likely to use a firearm or drug or poison ingestion than hanging. Findings suggest that the higher rate of suicide mortality among sexual minorities is likely driven by hanging, a method of suicide that is not particularly amenable to lethal method restricted-access prevention approaches. Future research directions, clinical training recommendations, and intervention opportunities are discussed.