Climate change mitigation strategies offer significant societal co-benefits such as improvement in public health, air quality, local economy, and even safety. By considering these co-benefits during the transportation planning process, local governments would be able to link their local appreciate mitigation actions into the Sustainable Development Goals (SDGs), where diverse objectives should be achieved simultaneously. This study first clarifies the co-benefits approach to climate change mitigation in the transport system, by introducing an integrated multiple-impact framework known as A-S-I (Avoid-Shift-Improve) to evaluate the co-benefits. Thereafter, it applies the quantitative modeling approach to assess public health and environmental co-benefits of the implementation of the Tehran Transportation Master Plan, “the TTMP” in the city of Tehran, Iran, which includes targeted interventions such as shifting from private vehicles to the urban transport system, improving vehicle technologies and introducing alternative fuels. The results from the application of “the TTMP” reveal a significant reduction of CO2 and other local air pollutant emissions by 12.9 and 1.4 million tons, respectively, prevention of about 10,000 mortality cases, and more than USD 35 million savings by 2030.