As homicide rates spike across the United States, researchers nominate diverse causes such as temperature, city greenness, structural racism, inequality, poverty and more. While variation in homicide rates clearly results from multiple causes, many correlation studies lack the systematic theory needed to identify the underlying factors that structure individual motivations. Building on pioneering work in evolutionary human sciences, we propose that when resources are unequally distributed, individuals may have incentives to undertake high-risk activities, including lethal violence, in order to secure material and social capital. Here we evaluate this theory by analysing federal data on homicide rates, poverty and income inequality across all 50 US states for the years 1990, 2000 and 2005–2020. Supporting predictions derived from evolutionary social sciences, we find that the interaction of poverty (scarcity) and inequality (unequal distribution) best explains variation in US homicide rates. Results suggest that the increase in homicide rates during the height of the COVID-19 pandemic are driven in part by these same underlying causes that structure homicide rates across the US over the last 30 years. We suggest that these results provide compelling evidence to expand strategies for reducing homicide rates by dismantling structures that generate and concentrate sustained poverty and economic inequality.