We performed seven and a half weeks of path-integrated concentration measurements of CO 2 , CH 4 , H 2 O, and HDO over the city of Boulder, Colorado. An open-path dual-comb spectrometer simultaneously measured time-resolved data across a reference path, located near the mountains to the west of the city, and across an over-city path that intersected two-thirds of the city, including two major commuter arteries. By comparing the measured concentrations over the two paths when the wind is primarily out of the west, we observe daytime CO 2 enhancements over the city. We then use a Gaussian plume model to estimate city emissions of on-road CO 2 as (6.9 ± 1.8) × 10 5 metric tons (MT) CO 2 /year, compared to the city bottom-up greenhouse gas inventory for the on-road vehicle sector of 4.5 × 10 5 MT CO 2 /year. The two values nearly agree to within the quoted uncertainty, which does not include additional systematic uncertainty associated in the temporal and spatial scaling of the given measurements to annual city-wide emissions. Finally, we discuss experimental modifications that could lead to improved estimates.