Surface ozone, a major air pollutant toxic to humans and damaging to ecosystems, is produced by the oxidation of volatile organic compounds in the presence of nitrogen oxides (NOx = NO + NO2) and sunlight. Climate warming may affect future surface ozone levels even in the absence of anthropogenic emission changes, but the direction of ozone change due to climate warming remains uncertain over the southeast US and other polluted forested areas. Here we use observations and simulations to diagnose the sensitivity of August surface ozone to large-scale temperature variations in the southeast US during 1988–2011. We show that the enhanced biogenic emissions and the accelerated photochemical reaction rates associated with warmer temperatures both act to increase surface ozone. However, the sensitivity of surface ozone to large-scale warming is highly variable on interannual and interdecadal timescales owing to variation in regional ozone advection. Our results have important implications for the prediction and management of future ozone air quality.