In this large, contemporary population-based analysis of SEER data (2015–2022) spanning >500 million person-years, never-married adults had consistently higher cancer incidence than ever-married individuals across nearly all cancer sites, demographic groups, and age categories. The excess risk was substantial—68% higher in men and 83% higher in women—and was most pronounced for cancers linked to infections (e.g., HPV), tobacco, and alcohol, while smaller for cancers such as breast, prostate, and thyroid. Associations strengthened with age and were particularly marked among Black men, although married Black men had lower incidence than married White men. Overall, marital status appears to function as a meaningful social determinant of cancer risk, likely reflecting cumulative behavioral, social, and healthcare-related exposures rather than a direct causal effect.