High ozone (O3) concentrations are a major concern for air quality in the São Paulo Metropolitan Area (SPMA). During 2016, the 8 hours state standard of 140 µg m–3 was exceeded on 32 days, whereas the 1-hour national standard of 160 µg m–3 was exceeded on 76 days. Exposure to such unhealthy O3 levels and other pollutants can lead to respiratory diseases. The focus of this study is to determine the main O3 precursor in terms of the volatile organic compounds (VOCs), in order to provide a scientific basis for control of this pollutant. In this work, 66 samples of hydrocarbons, 62 of aldehydes and 42 of ethanol were taken during the period from September 2011 to August 2012, from 7:00 to 9:00 a.m. The OZIPR trajectory model and SAPRC atmospheric chemical mechanism were used to determine the major O3 precursors. During the studied period, aldehydes represented 35.3% of the VOCs, followed by ethanol (22.6%), aromatic compounds (15.7%), alkanes (13.5%), ketones (6.8%), alkenes (6.0%) and alkadienes less than 0.1%. Considering the concentration of VOCs and their typical reactivity, the simulation results showed that acetaldehyde contributed to 61.2% of the O3 formation. Total aldehydes contributed 74%, aromatics (14.5%), alkenes (10.2%), alkanes (1.3%) and alkadienes (e.g., isoprene; 0.03%). Simulations results for the SPMA showed that the most effective alternative for limiting the O3 levels is to reduce the VOCs emissions, mainly the aldehydes.