The protection of pedestrians, cyclists, and public transportation passengers from environmental pollution is a global concern. This study fills the gap in the existing knowledge of temporal exposure to air pollution in Latin American metropolises. The paper proposes a methodology addressing the relationship between two objects of study, i.e., the users of active modes of transport and air quality. This new methodology assesses the spatiotemporal concurrence of both objects with statistical analysis of large open-access databases, to promote healthy and sustainable urban mobility. The application of the empirical methodology estimated the number of users of active transportation modes exposed to poor air quality episodes in the Guadalajara metropolitan area (Mexico) in 2019. The study considered two pollutants, ozone (O3) and particulate matter (PM10), and two active modes, cycling and bus rapid transit (BRT). Spatiotemporal analyses were carried out with geographic information systems, as well as with numeric computing platforms. First, big data were used to count the number of users for each mode within the area of influence of the air quality monitoring stations. Second, the number of air pollution episodes was obtained using the air quality index proposed by the Environmental Protection Agency (USA) on an hourly basis. Third, the spatiotemporal concurrence between air quality episodes and active mode users was calculated. In particular, the air quality monitoring data from the Jalisco Atmospheric Monitoring System were compared to users of the public bicycle share system, known as MiBici, and of a bus rapid transit line, known as Mi Macro Calzada. The results showed that the number of cyclists and BRT passengers exposed to poor air quality episodes was considerable in absolute terms, that is, 208,660 users, while it was marginal when compared to the total number of users exposed to better air quality categories in the study area, who represented only 10%. To apply the results at the metropolitan scale, the spatial distribution of the air quality monitoring system should be improved, as well as the availability of data on pedestrians and conventional bus passengers.