In 2019, approximately 20.8% of U.S. adults (50.6 million) reported using any tobacco product, with cigarettes being the most commonly used (14.0%). E-cigarettes were the most commonly used non-cigarette tobacco product (4.5%), particularly among adults aged 18–24 years (9.3%), where over half had never smoked cigarettes. The highest prevalence of tobacco use was observed among males, adults aged 25–44 years, non-Hispanic American Indian/Alaska Native adults, those with a General Educational Development (GED) certificate, those with an annual household income <$35,000, lesbian, gay, or bisexual (LGB) adults, uninsured adults, those with Medicaid, those with a disability, and those with mild, moderate, or severe generalized anxiety disorder. Comprehensive, evidence-based interventions, including tobacco price increases, smoke-free policies, media campaigns, and barrier-free cessation coverage, are recommended to reduce tobacco-related disease and death. Targeted interventions are also necessary to address subpopulations with higher tobacco use prevalence, which may vary by tobacco product type.In 2019, approximately 20.8% of U.S. adults (50.6 million) reported using any tobacco product, with cigarettes being the most commonly used (14.0%). E-cigarettes were the most commonly used non-cigarette tobacco product (4.5%), particularly among adults aged 18–24 years (9.3%), where over half had never smoked cigarettes. The highest prevalence of tobacco use was observed among males, adults aged 25–44 years, non-Hispanic American Indian/Alaska Native adults, those with a General Educational Development (GED) certificate, those with an annual household income <$35,000, lesbian, gay, or bisexual (LGB) adults, uninsured adults, those with Medicaid, those with a disability, and those with mild, moderate, or severe generalized anxiety disorder. Comprehensive, evidence-based interventions, including tobacco price increases, smoke-free policies, media campaigns, and barrier-free cessation coverage, are recommended to reduce tobacco-related disease and death. Targeted interventions are also necessary to address subpopulations with higher tobacco use prevalence, which may vary by tobacco product type.