Ground-level ozone is adverse to human and vegetation health. High ground-level ozone concentrations usually occur over the United States in the summer, often referred to as the ozone season. However, observed monthly mean ozone concentrations in the southeastern United States were higher in October than July in 2010. The October ozone average in 2010 reached that of July in the past three decades . Our analysis shows that this extreme October ozone in 2010 over the Southeast is due in part to a dry and warm weather condition, which enhances photochemical production, air stagnation, and fire emissions. Observational evidence and modeling analysis also indicate that another significant contributor is enhanced emissions of biogenic isoprene, a major ozone precursor, from water-stressed plants under a dry and warm condition. The latter finding is corroborated by recent laboratory and field studies. This climate-induced biogenic control also explains the puzzling fact that the two extremes of high October ozone both occurred in the 2000s when anthropogenic emissions were lower than the 1980s and 1990s, in contrast to the observed decreasing trend of July ozone in the region. The occurrences of a drying and warming fall, projected by climate models, will likely lead to more active photochemistry, enhanced biogenic isoprene and fire emissions, an extension of the ozone season from summer to fall, and an increase of secondary organic aerosols in the Southeast, posing challenges to regional air quality management.ground-level ozone | ozone season | regional climate change | isoprene | air quality G round-level ozone is a pollutant harmful to human and vegetation health (1, 2). High ground-level ozone events are typically found in the summer when the formation of ozone is active through photochemical reactions involving nitrogen oxides (NO x = NO + NO 2 ) and volatile organic compounds (VOCs). However, ozone concentrations are sensitive to weather and climate (3-8), and the high-ozone season could extend beyond summer in the future (9-13). Previous climate-chemistry model studies have estimated the change of ground-level ozone (ΔO 3 ) in the United States resulting only from meteorological changes. Their results show large variation in the sign and magnitude of ΔO 3 in the fall, especially over forested regions such as the southeastern United States (SE) (10, 13). The lack of consensus reflects the uncertainties in modeling regional climate change and the consequent response of ground-level ozone.In this study, we focus on analyzing the historical ozone records. Fig. 1A Fig. S1). The number increases to 324 exceedances at 112 stations if the new US ambient ozone standard threshold value, 70 ppbv, is used (SI Appendix, Fig. S1). The regional average reached 65 ppbv during October 8-10, 2010 ( Fig. 2A). ppbv, considerably lower than that in the summer ozone season (∼50 ppbv in July). However, in the two extreme years, 2000 and 2010, regional monthly mean [O 3 ] MDA8 are 52 and 49 ppbv, respectively, two interannual standa...