Isoprene is the predominant non-methane volatile organic compound emitted to the atmosphere and shapes tropospheric composition and biogeochemistry through its effects on ozone, other oxidants, aerosols, and the nitrogen cycle. Isoprene is emitted naturally by vegetation during daytime, when its photo-oxidation is rapid, and in the presence of nitrogen oxides (NOx) produces ozone and degrades air quality in polluted regions. Here, we show for a city downwind of an isoprene-emitting forest (St. Louis, MO) that isoprene actually peaks at night; ambient levels then endure, owing to low nighttime OH radical concentrations. Nocturnal chemistry controls the fate of that isoprene and the likelihood of a high-ozone episode the following day. When nitrate (NO3) radicals are suppressed, high isoprene persists through the night, providing photochemical fuel upon daybreak and leading to a dramatic late-morning ozone peak. On nights with significant NO3, isoprene is removed before dawn; days with low morning isoprene then have lower ozone with a more typical afternoon peak. This biogenic-anthropogenic coupling expands the daily high-ozone window and likely has an opposite O3-NOx response to what would otherwise be expected, with implications for exposure and air-quality management in cities that, like St. Louis, are downwind of major isoprene-emitting forests.