Alternative pathways for decarbonizing the United States (US) economy can have significantly different impacts on criteria air pollutants, including ozone and PM2.5. A version of the Global Change Analysis Model with state-level resolution (GCAM-USA) simulates the evolution of the US energy, agriculture, water, and land use systems and estimates the associated greenhouse gas (GHG) and air pollutant emissions. We developed a streamlined emissions scaling method linking state- and sector-level emissions estimates from GCAM-USA to the Community Multiscale Air Quality model (CMAQ) to examine their air quality impacts. We present results over the contiguous US for a reference scenario (Ref) of limited state and federal GHG actions for 2015–2050, and two CO2 mitigation scenarios, one using state-level CO2 reduction goals and vehicle electrification sales targets, and the second expanding them to the national level. In 2050, the mitigation scenarios reduce NOx and primary PM2.5 emissions by up to 55% and 24%, respectively, relative to 2015. Primary PM2.5 emissions increase under mitigation in some regions due to technology and fuel shifts to greater use of bioenergy and carbon capture and sequestration, suggesting the need to further manage pollutant emissions in the mitigation scenarios. CMAQ results for these mitigation scenarios show co-benefits US-wide of up to 4.1 ppb for maximum daily 8-h average ozone (May-to-September average), and up to 14.1 μg/m3 for PM2.5 (annual average). PM2.5 displays more spatial variability than ozone, consistent with the scenario emissions trends. Our methodology provides an efficient way to compare the air quality impacts of multiple energy alternatives.