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We estimated long-term tuberculosis (TB) trends in the US population and assessed prospects for TB elimination. We used a detailed simulation model allowing for changes in TB transmission, immigration, and other TB risk determinants. Five hypothetical scenarios were evaluated from 2017 to 2100: 1) maintain current TB prevention and treatment activities (base case); 2) provision of latent TB infection testing and treatment for new legal immigrants; 3) increased uptake of latent TB infection screening and treatment among high-risk populations, including a 3-month isoniazid-rifapentine regimen; 4) improved TB case detection; and 5) improved TB treatment quality. Under the base case, we estimate that by 2050, TB incidence will decline to 14 cases per million, a 52% (95% posterior interval (PI): 35, 67) reduction from 2016, and 82% (95% posterior interval: 78, 86) of incident TB will be among persons born …