The Wuhan Metropolitan Area, located in Central China, has experienced severe O3 pollution in recent years; thus urging to diagnose formation regime and propose reasonable control strategies. Multi-source data of air pollutants and meteorological factors in 4 cities during August 2019 when severe regional O3 pollution occurred were obtained; then, in-situ O3 formation mechanism, the O3-precursors sensitivity, the sources and control strategies of O3 were evaluated based on the combination of the 0-D photochemical observation-based model and the positive matrix factorization model through the analysis of local ozone budget, the relative incremental reactivity, an empirical kinetic model approach and source apportionment. The results indicated the P(O3) (net O3 production rate) was 25 ppbv h−1 in Ezhou and 11–13 ppbv h−1 in other 3 cities. The dominated photochemical production of O3 was NO + HO2 reaction (62–71%), whereas the main pathway to destroy O3 during daytime was NO2 + OH (>70%) and nocturnal loss of O3 with alkenes even reached up to 39–46%. Generally, O3 formation was sensitive to AVOC (Anthropogenic Volatile Organic Compounds), in which reactive aromatics, OVOCs (Oxygenated VOCs), and alkenes (xylenes, ethylene, isoprene, methyl vinyl ketone, hexanal, toluene and methacrolein, specifically) as well as abundant i-pentane should be targeted to alleviate O3 pollution. The highly reactive VOCs sources for O3 formation in this region were vehicular exhaust (28–41%), industrial emissions (20–29% except Ezhou), and solvent use (17–29% except Huangshi). Co-reduction of O3 precursors in aforementioned reactive emissions according to optimal ratios of AVOC to NO2, i.e., 5:1 (Wuhan and Huanggang), 4:1 (Ezhou), and 6:1 (Huangshi), could achieve local O3 effective mitigation. Surprisingly, P(O3) could reduce by 38% and 48% under 40% AVOC cut accompanied by NO2 in more contaminated cities (Wuhan and Ezhou). Overall, our study provides new insight to future collaborative O3 alleviation strategies formulation in Central China, which quantified O3 formation at different precursors levels in different cities suffering from regional O3 pollution, concluded best precursors control ratios and confirmed validity of O3 mitigation through precursors-oriented emission reduction in vital sources.