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This study used mathematical modeling to estimate the potential population-level impact of HSV-1 vaccination strategies in the United States. Infant vaccination with 70% efficacy and lifelong protection introduced in 2030 reduced oral and genital incidence rate by 47.3 and 58.3% by 2075, respectively, with annual new infections declining by 41.2 and 53.5%, corresponding to 28.5 million cumulative infections averted. The number needed to vaccinate to prevent one infection, defined from program initiation to a specified year, declined from 35.8 by 2040 to 7.2 by 2070. Addition of adolescent catch-up vaccination further reduced oral and particularly genital incidence. Lifelong protection produced approximately threefold greater impact than 15-year protection. 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