Antimicrobial resistance (AMR) is a growing global health threat that led to 1.27 million deaths in 2019. Given the widespread use of antimicrobials in healthcare, agriculture, and industrial applications and a range of factors affecting AMR, including demographic trends and physical climate risks, an economy-wide approach is essential to understand and assess the economic consequences of AMR. We model the global economic impacts of AMR under six alternative scenarios. These scenarios are designed to incorporate assumptions about changes in AMR-related disease incidence, the impact of a central scenario about future demographic change on AMR over time, and explore the sensitivity of assumptions about the effects of AMR on agriculture productivity. We also examine the additional impacts of changing climate risks on the evolution of AMR (focusing on one climate scenario), the consequences of changes in country risk premia due to the differential im-pacts of the evolution of AMR on countries, and the global economic impacts of changes in government expenditure in response to AMR. Our results find a significant global economic burden of worsening AMR due to demographic change and climate change risks, as well as significant eco-nomic benefits of taking action to address AMR. We emphasize that a “one-health” approach to managing AMR will have substantial economic benefits over the coming decades.