Abstract Background Sugar-sweetened beverage (SSB) consumption contributes to obesity, a risk factor for 13 cancers. Although SSB taxes can reduce intake, the health and economic impact on reducing cancer burdens in the United States are unknown, especially among low-income Americans with higher SSB intake and obesity-related cancer burdens. Methods We used the Diet and Cancer Outcome Model, a probabilistic cohort state-transition model, to project health gains and economic benefits of a penny-per-ounce national SSB tax on reducing obesity-associated cancers among US adults aged 20 years and older by income. Results A national SSB tax was estimated to prevent 22 075 (95% uncertainty interval [UI] = 16 040-28 577) new cancer cases and 13 524 (95% UI = 9841-17 681) cancer deaths among US adults over a lifetime. The policy was estimated to cost $1.70 (95% UI = $1.50-$1.95) billion for government implementation and $1.70 (95% UI = $1.48-$1.96) billion for industry compliance, while saving $2.28 (95% UI = $1.67-$2.98) billion cancer-related healthcare costs. The SSB tax was highly cost-effective from both a government affordability perspective (incremental cost-effectiveness ratio [ICER] = $1486, 95% UI = -$3516-$9265 per quality-adjusted life year [QALY]) and a societal perspective (ICER = $13 220, 95% UI = $3453-$28 120 per QALY). Approximately 4800 more cancer cases and 3100 more cancer deaths would be prevented, and $0.34 billion more healthcare cost savings would be generated among low-income (federal poverty-to-income ratio [FPIR] ≤ 1.85) than higher-income individuals (FPIR > 1.85). Conclusions A penny-per-ounce national SSB tax is cost-effective for cancer prevention in the United States, with the largest health gains and economic benefits among low-income Americans.