ImportanceSex disparities in physical activity (PA) and sports participation among US children and adolescents have been persistent. Quantifying the impact of reducing or eliminating these disparities may help determine how much to prioritize this problem and invest in interventions and policies to reduce them.ObjectiveTo quantify what might happen if existing PA and sports participation disparities were reduced or eliminated between male and female children and adolescents.Design, Setting, and ParticipantsThis simulation study used an agent-based model representing all children (aged 6 to 17 years) in the US, their PA and sports participation levels, and relevant physical and physiologic characteristics (eg, body mass index) as of 2023. Experiments conducted from April 5, 2024, to September 10, 2024, simulated what would happen during the lifetime of each cohort member if PA and sports participation levels for female participants were increased (to varying degrees) to match male participants in the same age group.Main Outcomes and MeasuresHealth outcomes, such as body mass index, incidence of weight-related conditions (eg, stroke, coronary heart disease, type 2 diabetes, and cancer), and economic outcomes (eg, direct medical costs and productivity losses).ResultsThis simulation study modeled 8 299 353 US children and adolescents (4 240 119 [51.1%] male and 4 059 234 [48.9%] female) aged 6 to 17 years. Eliminating PA sex disparities averted 28 061 (95% CI, 25 358-30 763) overweight and obesity cases per cohort by age 18 years, which in turn averted 4869 (95% CI, 4007-5732) weight-related disease cases during their lifetimes and resulted in recurring savings of $333.45 million (95% CI, $290.22 million to $376.68 million) in direct medical costs and $446.42 million (95% CI, $327.39 million to $565.44 million) in productivity losses (in 2024 US dollars) for every new cohort of 6- to 17-year-olds. Reducing PA disparities by 50% averted 9027 (95% CI, 6942-11 112) overweight and obesity cases. Eliminating sex disparities in sports participation averted 41 499 (95% CI, 37 874-45 125) cases of overweight and obesity and 8939 (95% CI, 8088-9790) weight-related disease cases during their lifetimes, generating recurring savings of $713.48 million (95% CI, $668.80 million to $758.16 million) in direct medical costs and $839.68 million (95% CI, $721.18 million to $958.18 million) in productivity losses.Conclusions and RelevanceIn this simulation study of youth PA and sports participation, eliminating sex disparities could save millions of dollars for each new cohort of 6- to 17-year-olds, which could exceed the cost of programs and investments that could enable greater equity.