Slowing climate change is crucial to the future wellbeing of human societies and the greater environment. Current beef production systems in the USA are a major source of negative environmental impacts and raise various animal welfare concerns. Nevertheless, beef production provides a food source high in protein and many nutrients as well as providing employment and income to millions of people. Cattle farming also contributes to individual and community identities and regional food cultures. Novel plant-based meat alternatives have been promoted as technologies that could transform the food system by reducing negative environmental, animal welfare, and health effects of meat production and consumption. Recent studies have conducted static analyses of shifts in diets globally and in the USA, but have not considered how the whole food system would respond to these changes, nor the ethical implications of these responses. We aimed to better explore these dynamics within the US food system and contribute a multiple perspective ethical assessment of plant-based alternatives to beef.In this national modelling analysis, we explored multiple ethical perspectives and the implications of the adoption of plant-based alternatives to beef in the USA. We developed USAGE-Food, a modified version of USAGE (a detailed computable general equilibrium model of the US economy), by improving the representation of sector interactions and dependencies, and consumer behaviour to better reflect resource use across the food system and the substitutability of foods within households. We further extended USAGE, by linking estimates of the environmental footprint of US agriculture, to estimate how changes across the agriculture sector could alter the environmental impact of primary food production across the whole sector, not only the beef sector. Using USAGE-Food, we simulated four beef replacement scenarios against a baseline of current beef demand in the USA: BEEF10, in which beef expenditure is replaced by other foods and three scenarios wherein 10%, 30%, or 60% of beef expenditure is replaced by plant-based alternatives.The adoption of plant-based beef alternatives is likely to reduce the carbon footprint of US food production by 2·5-13·5%, by reducing the number of animals needed for beef production by 2-12 million. Impacts on other dimensions are more ambiguous, as the agricultural workforce and natural resources, such as water and cropland, are reallocated across the food system. The shifting allocation of resources should lead to a more efficient food system, but could facilitate the expansion of other animal value chains (eg, pork and poultry) and increased exports of agricultural products. In aggregate, these changes across the food system would have a small, potentially positive, impact on national gross domestic product. However, they would lead to substantial disruptions within the agricultural economy, with the cattle and beef processing sectors decreasing by 7-45%, challenging the livelihoods of the more than 1·5 million people currently employed in beef value chains (primary production and animal processing) in the USA.Economic modelling suggests that the adoption of plant-based beef alternatives can contribute to reducing greenhouse gas emissions from the food system. Relocation of resources across the food system, simulated by our dynamic modelling approach, might mitigate gains across other environmental dimensions (ie, water or chemical use) and might facilitate the growth of other animal value chains. Although economic consequences at the country level are small, there would be concentrated losses within the beef value chain. Reduced carbon footprint and increased resource use efficiency of the food system are reasons for policy makers to encourage the continued development of these technologies. Despite this positive outcome, policy makers should recognise the ethical assessment of these transitions will be complex, and should remain vigilant to negative outcomes and be prepared to target policies to minimise the worst effects.The Stavros Niarchos Foundation, the Bill & Melinda Gates Foundation, Johns Hopkins University, the Commonwealth Scientific and Industrial Research Organisation, Cornell University, and Victoria University.