The efficacy of influenza vaccines, currently at 44%, is limited by the rapid antigenic evolution of the virus and a manufacturing process that can lead to vaccine mismatch. The National Institute of Allergy and Infectious Diseases (NIAID) recently identified the development of a universal influenza vaccine with an efficacy of at least 75% as a high scientific priority. The US Congress approved $130 million funding for the 2019 fiscal year to support the development of a universal vaccine, and another $1 billion over 5 y has been proposed in the Flu Vaccine Act. Using a model of influenza transmission, we evaluated the population-level impacts of universal influenza vaccines distributed according to empirical age-specific coverage at multiple scales in the United States. We estimate that replacing just 10% of typical seasonal vaccines with 75% efficacious universal vaccines would avert ～5.3 million cases, 81,000 hospitalizations, and 6,300 influenza-related deaths per year. This would prevent over $1.1 billion in direct health care costs compared to a typical season, based on average data from the 2010-11 to 2018-19 seasons. A complete replacement of seasonal vaccines with universal vaccines is projected to prevent 17 million cases, 251,000 hospitalizations, 19,500 deaths, and $3.5 billion in direct health care costs. States with high per-hospitalization medical expenses along with a large proportion of elderly residents are expected to receive the maximum economic benefit. Replacing even a fraction of seasonal vaccines with universal vaccines justifies the substantial cost of vaccine development.