PM2.5 and O3 controls are traditionally considered separately because PM2.5 is usually high in winter while O3 is generally high in summer. In this study, we explore the opportunity of controlling the two pollutants simultaneously through a better understanding of their intra-seasonal correlation and chemical-coupling behaviors under different meteorological conditions during the late summer and early fall (August–September) episodes in the San Joaquin Valley (SJV), California. A correlation analysis is first used to identify the temporal correlations between O3 and PM2.5 and their underlying physical and chemical drivers. Sensitivity analysis is then applied to determine the chemical coupling between PM2.5 and O3 and subsequent multipollutant control opportunities under two contrasting meteorological conditions using the Community Multi-Scale Air Quality (CMAQ) model. We find that O3 and PM2.5 are positively correlated on the daily timescale because both are sensitive to atmospheric stagnation. However, O3 and PM2.5 are negatively correlated on the hourly timescale determined by the negative correlation between hourly NO3− and O3, which is mainly due to the opposite effects of T and RH on the diurnal variations of NO3− and O3. Reducing NOx on average lead to O3 increase, but it can facilitate reducing O3 at higher O3 (>75 ppb) locations under the more stagnant conditions. NOx emission control could become beneficial for both O3 and PM2.5 when the NOx emissions in 2005 are further reduced by 15% under the more stagnant meteorological conditions and by 30% under the more ventilated meteorological conditions.