Sexual minorities (SM) have higher chronic physiologic stress as indicated by allostatic load (AL), which may be explained in part by consistent experiences of discriminatory practices. This is one of the first studies to examine the joint effects of SM status and AL on the association with long-term risk for cancer death. Retrospective analyses were conducted on 12,470 participants using National Health and Nutrition Examination Survey (NHANES) from years 2001 through 2010 linked with the National Death Index through December 31, 2019. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) of cancer deaths between groups of SM (those reporting as gay, lesbian, bisexual, or having same-sex sexual partners) status and AL. SM adults living with high AL (n= 326) had a 2-fold increased risk of cancer death (aHR: 2.55, 95% CI: 1.40–4.65) when compared to straight/heterosexual adults living with low AL (n= 6674). Among those living with high AL, SM (n= 326) had a 2-fold increased risk of cancer death (aHR: 2.26, 95% CI: 1.33–3.84) when compared to straight/heterosexual adults with high AL (n= 4957). SM with high AL have an increased risk of cancer mortality. These findings highlight important implications for promoting a focused agenda on cancer prevention with strategies that reduce chronic stress for SM adults.