Governments worldwide have pledged to reduce antimicrobial use in the agri-food system. This study projects global livestock antibiotic use quantities through 2040 under various scenarios. This work indicates that under a business-as-usual scenario, global antibiotic use could reach ~143,481 tons by 2040, representing a 29.5% increase from the 2019 baseline of ~110,777 tons. However, alternative scenarios suggest that these projections could vary by +14.2% to -56.8%, depending on changes in livestock biomass and antibiotic use intensity. A key contribution of this research is the development of the Livestock Biomass Conversion method, a novel indicator offering improved accuracy in estimating livestock biomass. The findings have important policy implications, highlighting that meaningful reductions in antibiotic use quantity can only be achieved through coordinated efforts targeting both antibiotic use intensity and livestock biomass. Global commitments to reducing antimicrobial use in agrifood systems underscore the urgent need to address antimicrobial resistance. Here, the authors project changes in antibiotic use in livestock through 2040, exploring various potential pathways