In this paper, we use origin and destination mobility surveys and high-resolution assignment and emission models to study air quality and short-lived climate pollutant impacts related to on-road transportation in the Metropolitan Area of São Paulo (MASP). To begin with, we calculate transport carbon dioxide (CO2) emissions from fossil fuel-driven vehicles (light and heavy-duty) at spatial and temporal resolutions of 500 m and one hour, by means of traffic demand forecasting. These estimates, carry out for 2007 and 2012, are based on passenger and freight trips and the height of the atmospheric boundary layer, among other variables. These proxies depend also on ancillary parameters as particulate matter concentrations and dilution rates. In the second place, we evaluate the changes in CO2 emissions from the MASP (3%/year). Transport emission inventories combine mobility surveys and road network assignments with air quality data. In spite of using different methodologies, bottom-up road link assignments versus top-down vehicle activity-based and fuel consumption approaches, the estimated CO2 emissions are consistent with the Official São Paulo State's Inventory. This work found that the CO2 emissions in MASP were 10,044 and 11,503 t Ceq./day in 2007 and 2012 (73% light and 27% heavy vehicles), respectively. On-road emission patterns agree with the spatial-temporal variation of transportation journeys and corresponding passenger and freight network assignments. Temporal patterns, diurnal, weekly and monthly, were determined using traffic counts and congestion surrogates. The patterns were also crosschecked with average CO2 measurements, available for 2014 at the road (western area of MASP) and background sites (Jaraguá Peak). Kerbside road measurements showed two prominent peaks associated to the morning (437 ± 45 ppm) and night rush hours (435 ± 49 ppm), coupled to low values of boundary layer height (313 m) and dilution rate (329 m2/h). Background values (414 ± 2 ppm) were subtracted from on-road measurements to estimate excess CO2 (12 ± 8 ppm) directly attributed to vehicles. The inventory reflects the relationships between traffic patterns and emissions, and the developed methodology could be used to evaluate the impacts of forthcoming urban transport and emission control policies. In the future, our estimates will be verified with ground measurements of CO2 concentrations over a bigger monitoring network in the MASP.