Agriculture is essential for feeding the large and growing world population, but it can also generate pollution that harms ecosystems and human health. Here, we explore the human health effects of air pollution caused by the production of maize—a key agricultural crop that is used for animal feed, ethanol biofuel and human consumption. We use county-level data on agricultural practices and productivity to develop a spatially explicit life-cycle-emissions inventory for maize. From this inventory, we estimate health damages, accounting for atmospheric pollution transport and chemistry, and human exposure to pollution at high spatial resolution. We show that reduced air quality resulting from maize production is associated with 4,300 premature deaths annually in the United States, with estimated damages in monetary terms of US$39 billion (range: US$14–64 billion). Increased concentrations of fine particulate matter (PM2.5) are driven by emissions of ammonia—a PM2.5 precursor—that result from nitrogen fertilizer use. Average health damages from reduced air quality are equivalent to US$121 t−1 of harvested maize grain, which is 62% of the US$195 t−1 decadal average maize grain market price. We also estimate life-cycle greenhouse gas emissions of maize production, finding total climate change damages of US$4.9 billion (range: US$1.5–7.5 billion), or US$15 t−1 of maize. Our results suggest potential benefits from strategic interventions in maize production, including changing the fertilizer type and application method, improving nitrogen use efficiency, switching to crops requiring less fertilizer, and geographically recating production.