Limited information exists on whether associations between substance use behaviors (SUBs) and sexual risk behaviors (SRBs) vary by sexual identity. Data from the 2015 national Youth Risk Behavior Survey (n = 15,624), were analyzed to assess associations between SUBs (cigarette smoking, alcohol use, binge drinking, marijuana use, prescription drug misuse, injection drug use, illicit drug use) and SRBs (sexual activity, number of partners, condom use). Logistic regression models calculated adjusted prevalence ratios (aPR), stratified by sexual identity, and interaction effects for sexual identity were introduced to models to determine if associations varied by sexual identity. All SUBs had significant associations with current sexual activity and 4+ sexual partners for both heterosexual and LGB students. No condom use during last sexual intercourse was significantly associated with all SUBs except alcohol use among heterosexual students, while no condom use was only significantly associated with injection drug use among LGB students. Associations between current sexual activity and SUBs were significantly stronger among heterosexual compared to LGB students for smoking (aPR = 2.39;95% CI:2.15,2.65 vs aPR = 1.49;95% CI:1.14,1.95), marijuana use (2.41;2.15,2.71 vs 1.86;1.58,2.19) and prescription drug misuse (2.10;1.93,2.28 vs 1.60;1.28,2.00). Associations between no condom use and SUBs were significantly stronger for heterosexual compared to LGB students only for smoking (1.32;1.16,1.50 vs 0.96;0.73,1.25) and marijuana use (1.22;1.07,1.38 vs 0.90;0.72,1.12). The relationship between most SUBs and SRBs did not vary significantly by sexual identity. These findings underscore the importance coordinating school-based programs to prevent substance use and promote sexual health.