Here, we present an assessment of long-term trends in the O3 weekend effect (WE) occurrences and spread within the Mexico City (MCMA), Guadalajara (GMA), and Monterrey (MMA) metropolitan areas, which are the three largest metropolitan areas (MAs) of Mexico and concentrate around 33% of the total population in the country. Daytime averages and peak differences in O3 concentrations from weekdays to weekends were used as a proxy of WE occurrence. All MAs exhibited the occurrence of WE in all years at least in one monitoring site. Substantial differences in O3 daytime averages and peaks from weekdays to weekends have decreased over time in all MAs, and since 1998 and 2013 for the MCMA and GMA, respectively, higher O3 levels during weekends are typical during most of the year. The largest variations in the O3 WE were observed at downwind and urban core sites of the MCMA and GMA. Significant increasing trends (p < 0.05) in the O3 WE magnitude were observed for Sundays at all sites within the MCMA, with trends in annual averages ranging between 0.33 and 1.29 ppb O3 yr−1. Within the GMA, for Sundays, fewer sites exhibited increasing trends in the WE occurrence and at lower growth rates (0.32 and 0.48 ppb yr−1, p < 0.1) than within the MCMA, while within the MMA no apparent trends were observed in marked contrast with the MCMA and GMA. Our findings suggest that policies implemented have been successful in controlling weekday ground-level O3 within the MCMA and GMA, but further actions must be introduced to control the increases in the O3 WE magnitude and spread.