Heavily advertised as a harmless tobacco alternative, hookah (i.e., waterpipe)-flavored tobacco smoking has contributed to the wider epidemic of smoking, especially amongst marginalized sexual minority (SM) populations. Evidence regarding the concurrent use of substances and other drugs, among SM current hookah smokers, is scarce. We utilized nationally representative data from the Population Assessment of Tobacco and Health (PATH) Study (2016–2019) to examine patterns of the concurrent use of substances (i.e., marijuana, painkillers, sedatives, tranquilizers, cocaine, stimulants (specifically methamphetamines), and others), in SM adult hookah smokers and their heterosexual counterparts. Current hookah smoking is higher among SM adults (Wave 4: 4.22% [95% CI = 2.94–5.94] and Wave 5: 2.65% [95% CI = 1.81–3.48]) than heterosexuals (Wave 4: 1.31% [95% CI = 1.13–1.50] and Wave 5: 1.07% [95% CI = 0.89–1.25]). Among current SM hookah users, the co-use of substances, including alcohol, marijuana, and cocaine, is comparable to heterosexuals (p = ns). Adjusting for gender alone and all covariates, including age, sex, race/ethnicity, education, income, and education, no differences in concurrent substance use were observed between SM and heterosexual hookah users. While the co-use of substances is comparable between SM and heterosexual hookah smoker adults, the prevalence of current hookah use more than doubled among SM individuals than heterosexual individuals during 2018–2019. Our findings highlight the critical value of prevention efforts directed to increase education and awareness about hookah smoking use and known health effects, particularly tailored towards sexual minorities.