Health risks from air pollution continue to be a major concern for residents in Mexico City. These health burdens could be partially alleviated through individual avoidance behavior if accurate information regarding the daily health risks of multiple pollutants became available. A split sample approach was used in this study to create and validate a multi-pollutant, health-based air quality index. Poisson generalized linear models were used to assess the impacts of ambient air pollution (i.e., fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ground-level ozone (O3)) on a total of 610,982 daily emergency department (ED) visits for respiratory disease obtained from 40 facilities in the metropolitan area of Mexico City from 2010 to 2015. Increased risk of respiratory ED visits was observed for interquartile increases in the 4-day average concentrations of PM2.5 (Risk Ratio (RR) 1.03, 95% CI 1.01–1.04), O3 (RR 1.03, 95% CI 1.01–1.05), and to a lesser extent NO2 (RR 1.01, 95% CI 0.99–1.02). An additive, multi-pollutant index was created using coefficients for these three pollutants. Positive associations of index values with daily respiratory ED visits was observed among children (ages 2–17) and adults (ages 18+). The use of previously unavailable daily health records enabled an assessment of short-term ambient air pollution concentrations on respiratory morbidity in Mexico City and the creation of a health-based air quality index, which is now currently in use in Mexico City.