Drought conditions affect ozone air quality, potentially altering multiple terms in the O3 mass balance equation. Here, we present a multiyear observational analysis using data collected before, during, and after the record-breaking California drought (2011-2015) at the O3-polluted locations of Fresno and Bakersfield near the Sierra Nevada foothills. We separately assess drought influences on O3 chemical production ( PO3) from O3 concentration. We show that isoprene concentrations, which are a source of O3-forming organic reactivity, were relatively insensitive to early drought conditions but decreased by more than 50% during the most severe drought years (2014-2015), with recovery a function of location. We find drought-isoprene effects are temperature-dependent, even after accounting for changes in leaf area, consistent with laboratory studies but not previously observed at landscape scales with atmospheric observations. Drought-driven decreases in organic reactivity are contemporaneous with a change in dominant oxidation mechanism, with PO3 becoming more NO x-suppressed, leading to a decrease in PO3 of ∼20%. We infer reductions in atmospheric O3 loss of ∼15% during the most severe drought period, consistent with past observations of decreases in O3 uptake by plants. We consider drought-related trends in O3 variability on synoptic time scales by analyzing statistics of multiday high-O3 events. We discuss implications for regulating O3 air pollution in California and other locations under more prevalent drought conditions.